First clinical trial of gene therapy for muscular dystrophy now under way

The first gene therapy human trial in the United States for a form of muscular dystrophy is under way.
The clinical trial for Duchenne muscular dystrophy (DMD) tests the safety and effectiveness of a therapy that was developed over two decades by scientists at the University of North Carolina at Chapel Hill's School of Medicine and the University of Pittsburgh.
The trial was launched March 28, at Columbus Children's Hospital in Ohio, an affiliate of Ohio State University's School of Medicine. In the trial, six boys with DMD will receive replacement genes for an essential muscle protein.
Each of the boys will receive replacement genes via injection into a bicep of one arm and a placebo in the other arm. Neither the investigators nor the participants will know which muscle got the genes. After several weeks, an analysis of the injected muscle tissue's microscopic appearance, as well as extensive testing of the health and strength of the trial participants, will reveal whether gene therapy for DMD is likely to be safe and whether it's likely to result in persistent production of the essential protein in muscle cells.

Read the complete article here

Researchers get neurons and silicon talking

From EurekAlert:
The ultimate applications are potentially limitless. In the long term it will possibly enable the creation of very sophisticated neural prostheses to combat neurological disorders. What's more, it could allow the creation of organic computers that use living neurons as their CPU.
Those applications are potentially decades away, but in the much nearer term the new technology could enable very advanced and sophisticated drug screening systems for the pharmaceutical industry.
"Pharmaceutical companies could use the chip to test the effect of drugs on neurons, to quickly discover promising avenues of research," says Professor Stefano Vassanelli, a molecular biologist with the University of Padua in Italy, and one of the partners in the NACHIP project, funded under the European Commission's Future and Emerging Technologies initiative of the IST programme.
NACHIP's core achievement was to develop a working interface between the living tissue of individual neurons and the inorganic compounds of silicon chips. It was a difficult task.
"We had a lot of problems to overcome," says Vassanelli. "And we attacked the problems using two major strategies, through the semiconductor technology and the biology."
With the help of German microchip company Infineon, NACHIP placed 16,384 transistors and hundreds of capacitors on a chip just 1mm squared in size. The group had to find appropriate materials and refine the topology of the chip to make the connection with neurons possible.
Biologically NACHIP uses special proteins found in the brain to essentially glue the neurons to the chip. These proteins act as more than a simple adhesive, however. "They also provided the link between ionic channels of the neurons and semiconductor material in a way that neural electrical signals could be passed to the silicon chip," says Vassanelli.
Once there, that signal can be recorded using the chip's transistors. What's more, the neurons can also be stimulated through the capacitors. This is what enables the two-way communications.
The project tested the device by stimulating the neurons and recording which ones fired using standard neuroscience techniques while tracking the signals coming from the chip.
The development of the interface and chip are crucial for this new technology, but problems remain. "Right now, we need to refine the way we stimulate the neurons, to avoid damaging them," says Vassanelli.
That's one of the problems the team hopes to tackle in a future project. Right now a proposal has been prepared which could tackle this and many other problems, including how to communicate with the neurons using genes.
"Genes are where memory come from, and without them you have no memory or computation. We want to explore a way to use genes to control the neuro-chip," says Vassanelli.
If NACHIP took the first crucial step towards a neuron-powered CPU, future work will pave the way for a genetically-powered hard disk.
"Europe is very well placed in this field of research, because it is essentially a multidisciplinary field, and we have multidisciplinary teams working on it," says Vassanelli. "We also have the infrastructure with institutes like the Max Planck Institute for Biochemistry in Martinsried, which is one of the world leaders in the field. Europe should be very proud of these resources. It gives us access to equipment and expertise that would be very hard to replicate elsewhere."

Arthritis

The Houston Chronicle is running an article on the tissue engineering of new cartilage as a brute force therapy for the age-related damage of arthritis: "I have been researching this area of cartilage since 1984, and this is the most excited I have ever been about the work ... Athanasiou's group describes the first successful method of growing and molding cartilage into natural forms without requiring scaffolds, trellis-like arrangements upon which cells are seeded and grown. ... Using nothing but cartilage donor cells, Athanasiou's group grew dime-sized disks of cartilage nearly identical to that in the body. ... We're no longer talking about repairing a small lesion. Potentially, we're talking about effectively treating osteoarthritis by resurfacing the entire joint. I'm not saying we're there yet, but we're beginning to see that it's doable."

View the Article Under Discussion: http://www.chron.com/disp/story.mpl/health/3747377.html
Read More Longevity Meme Commentary: http://www.longevitymeme.org/news/

Reduced insulin in the brain triggers Alzheimer's degeneration

Neuroendocrine disorder distinct from other types of diabetes
Providence, RI – By depleting insulin and its related proteins in the brain, researchers at Rhode Island Hospital and Brown Medical School have replicated the progression of Alzheimer's disease – including plaque deposits, neurofibrillary tangles, impaired cognitive functioning, cell loss and overall brain deterioration – in an experimental animal model. The study demonstrates that Alzheimer's is a brain-specific neuroendocrine disorder, distinct from other types of diabetes.
In the study, brain deterioration was not related to the pancreas, which regulates insulin for the body. When pancreatic insulin is deficient or the body fails to respond to it, the result is Type 1 or Type 2 diabetes. Previous work by the researchers with postmortem brain tissue of Alzheimer's patients showed a strong link between insulin depletion in the brain and Alzheimer's disease, raising the possibility that Alzheimer's is a neuroendocrine disorder, or a Type 3 diabetes.
"We have demonstrated that a loss of insulin in the brain triggers the onset of Alzheimer's, probably because as the brain loses insulin, the cells that require insulin to function and survive also eventually die. The consequences are increased oxidative stress, brain deterioration, loss of cognitive function, and a buildup of plaques and tangles in the brain – all hallmarks of Alzheimer's, says senior author Suzanne M. de la Monte, MD, MPH, a neuropathologist at Rhode Island Hospital and a professor of pathology and clinical neuroscience at Brown Medical School in Providence, RI.
"We now know that if you specifically target insulin and its actions in the brain, you could develop new treatments for this disease," de la Monte says.
The study is published in the current issue (Volume 9, Issue 1) of the Journal of Alzheimer's Disease (http://www.j-alz.com).
Researchers injected the brains of rats with Streptozotocin (STZ), a compound that when metabolized, destroys beta cells in pancreatic islets and produces diabetes. When injected directly into the brain, the treatment caused neurodegeneration, while the pancreatic islet cells remained intact. That is because insulin depletion produced by STZ was confined to the brain, just like what occurs in most cases of Alzheimer's.
"This study provides definitive evidence that impairments in insulin/IGF signaling and deficiencies in the corresponding growth factors can occur in the central nervous system (CNS) independent of Type 1 or Type 2 diabetes," the authors write.
As a result of the treatment, insulin and its IGF-I receptors were significantly reduced in the brain, triggering a cascade of neurodegeneration. Both insulin and IGF-I activate complex signaling pathways downstream, prompting energy metabolism and growth required for learning and memory, and inhibition of oxidative stress, which unchecked could trigger neurodegeneration. As insulin was depleted, neurons died and the brain dropped to half its size, a result of atrophy which is a prominent feature of Alzheimer's. At the same time, there was an increase in astrocytes and microglial cells, which are responsible for neuroinflammation, another critical and consistent feature of Alzheimer's and probably related to the increased amyloid deposition in the brain, the researchers say.
Also, there was increased activation of a kinase called GSK-3 beta. This kinase is overactive in Alzheimer's and triggers tau phosphorylation, which is known to be at the core of neurofibrillary tangles. The researchers had previously shown that tau is regulated by insulin and insulin-like growth factor (IGF-I). In the current research, they found that as insulin and IGF-I were depleted in the brain, the expression of GSK-3 beta increased, leading to oxidative stress and cell death.
While the link between insulin and tau had been established, researchers also looked at the connection between insulin and amyloid precursor protein gene expression, as increased levels could account for amyloid accumulation, or the buildup of plaques in the brain. They found that amyloid beta deposits in vessels and plaques did build up in the brain, and they suggest that these abnormalities occurred due to increased oxidative stress.
Another feature of Alzheimer's affected by impaired insulin signaling, acetylcholine deficiency, is linked to dementia and has long recognized as an early abnormality in Alzheimer's. The enzyme that makes acetylcholine, choline acetyltransferase (ChAT), was previously found to be regulated by insulin and IGF-1. In brains with Alzheimer's, impairment of insulin and IGF-I signaling mechanisms correlate with deficits in acetylcholine production. In this study, ChAT was markedly reduced in the experimental Alzheimer's model.
"Our previous work has shown that many of the important features of Alzheimer's – such as the accumulation of phosphorylated tau and the death of neurons – were somehow linked to insulin deficiency in the brain. This study shows that insulin is the controlling factor in all of these features of Alzheimer's disease," de la Monte says.
"The evidence suggests that impaired insulin and IGF signaling must be addressed in order to make significant progress in the treatment and prevention of Alzheimer's disease," she says.

Scientists One Step Closer To Cancer Vaccine

Scientists at Karolinska Institutet in Sweden have helped to identify a molecule that can be used as a vaccination agent against growing cancer tumours. Although the results are so far based on animal experiments, they point to new methods of treating metastases.
The results are presented in the online edition of the prestigious scientific journal Nature Medicine, and represent the collaborative efforts of researchers at KI and Leiden University Medical Centre in Holland.
The study analysed an immunological cell, a T cell, which recognises other cells with defects common to metastasing ones. These defects (which are found in MHC class 1 molecules) allow the tumour cell to evade the "conventional" T cell-mediated immune defence.
The researchers have identified a short peptide molecule that the T cell in the study recognises. Using this peptide, the researchers can vaccinate and protect against the spread of tumours from different tissues, including melanoma, colon cancer, lymphoma, and fibrosarcoma.
"So far we've only conducted research on mice, so it's too early to get out hopes up too much," says research scientist Elisabeth Wolpert at the Microbiology and Tumour Biology Centre. "However, the study does point towards new possible ways of developing a treatment for advanced tumour diseases."
The newly published study is a continuation of an original discovery that first identified the TEIPP-T cell and that was presented in Ms Wolpert's doctoral thesis at Karolinska Institutet in 1998.
The spread of tumours, or metastases, is the most common cause of death from cancer.

Publication: Selective cytotoxic T-lymphocyte targeting of tumor immune escape variants, Nature Medicine, AOP (online edition), Thorbald van Hall, Elisabeth Wolpert, Peter van Veelen, Klas Kärre, Hans-Gustaf Ljunggren, Cornelis JM Melief, Rienk Offringa, et al.

The original news release can be found here.

Scientists one step closer to cancer vaccine

Scientists at Karolinska Institutet in Sweden have helped to identify a molecule that can be used as a vaccination agent against growing cancer tumours. Although the results are so far based on animal experiments, they point to new methods of treating metastases.
The results are presented in the online edition of the prestigious scientific journal Nature Medicine, and represent the collaborative efforts of researchers at KI and Leiden University Medical Centre in Holland.
The study analysed an immunological cell, a T cell, which recognises other cells with defects common to metastasing ones. These defects (which are found in MHC class 1 molecules) allow the tumour cell to evade the "conventional" T cell-mediated immune defence.
The researchers have identified a short peptide molecule that the T cell in the study recognises. Using this peptide, the researchers can vaccinate and protect against the spread of tumours from different tissues, including melanoma, colon cancer, lymphoma, and fibrosarcoma.
"So far we've only conducted research on mice, so it's too early to get out hopes up too much," says research scientist Elisabeth Wolpert at the Microbiology and Tumour Biology Centre. "However, the study does point towards new possible ways of developing a treatment for advanced tumour diseases."
The newly published study is a continuation of an original discovery that first identified the TEIPP-T cell and that was presented in Ms Wolpert's doctoral thesis at Karolinska Institutet in 1998.
The spread of tumours, or metastases, is the most common cause of death from cancer.

###

Publication: Selective cytotoxic T-lymphocyte targeting of tumor immune escape variants, Nature Medicine, AOP (online edition), Thorbald van Hall, Elisabeth Wolpert, Peter van Veelen, Klas Kärre, Hans-Gustaf Ljunggren, Cornelis JM Melief, Rienk Offringa, et al
For further information, contact:
Elisabeth Wolpert on +46-70-7658308 or at elisabeth.wolpert@ki.se
Katarina Sternudd, KI Press Officer, on +46-8-524 838 95, +46-70- 224 38 95 or at katarina.sternudd@ki.se
via [EurekAlert!]

Astonishing Advances in Tissue Regeneration

By Heather S. Oliff, PhD
A Genetic Approach to Regeneration
Researchers at the Wistar Institute in Philadelphia, PA, are studying a unique strain of mouse that can heal wounds by regeneration. After a hole is pierced in the mouse’s ear (a typical laboratory identification procedure), it closes with no evidence that a hole was ever present.¹⁶ These animals, known as Murphy/Roths/Large mice, or MRL mice, are so named to denote the two scientists who originally bred them, as well as their unusually large size. MRL mice are genetically unique, and scientists are researching them to elucidate the genetics of regeneration, hoping to gather information that can be used to help humans.¹⁷
When the Wistar scientists induced heart injury in both MRL mice and typical mice, they found that the MRL mouse heart returned to normal, whereas the typical mouse heart was scarred.¹⁸ Human hearts scar following injury from heart attack, and the scarring response contributes to chronic heart disease and death.¹⁹ The healing response in the MRL mouse, however, differed greatly from that of the typical mouse. The MRL mouse displayed early movement of cardiomyocytes into the wound site, and DNA synthesis and proliferation of these cells.¹⁸ The MRL mouse heart also demonstrated better revascularization (restoration of blood supply) at the site of injury, which is necessary to help cells thrive and avoid death. According to the scientists, the MRL mouse studies demonstrate that “mammalian hearts have significant capacity to regenerate.”¹⁸
The Wistar scientists are now working to identify which genetic and biochemical factors are involved in this regenerative response. They have already identified areas on several chromosomes that control wound closure and are involved in regeneration of the MRL mouse ear tissue.^19,20 It is unclear whether these same chromosomes are responsible for regenerating the MRL heart.¹⁸
A potential key mediator of regeneration is the family of enzymes known as the matrix metalloproteinases. These protein-digesting enzymes degrade the collagen that helps form scar tissue. They occur in immune cells, along with another family of molecules called the tissue inhibitors of metalloproteinase, which inhibit matrix metalloproteinases. After an injury, neutrophils that contain matrix metalloproteinases and tissue inhibitors of metalloproteinase enter the wound. Regeneration or scarring occurs depending on whether matrix metalloproteinases or tissue inhibitors of metalloproteinase dominate. The MRL mouse ear wound has a more active form of matrix metalloproteinases and lower levels of tissue inhibitors of metalloproteinase than the typical mouse ear wound.¹⁹ This combination promotes a regeneration process rather than a scarring process in the MRL mouse.¹⁹
The scientists also looked at the ability of MRL mice to heal central nervous system injuries.²² In the MRL mice, the matrix metalloproteinase response was temporarily increased following a brain injury, but the brain was not repaired differently than that of the typical mouse.²² The researchers hypothesize that the central nervous system has mechanisms to decrease the matrix metalloproteinase response, and that the tendency to scar blocks regenerative healing.^17,19,22 Discovering how to prevent the formation of scar tissue may eventually make it possible to regenerate the heart, heal chronic wounds and burns, repair spinal tissue, and promote organ replacement.

References
16. Clark LD, Clark RK, Heber-Katz E. A new murine model for mammalian wound repair and regeneration. Clin Immunol Immunopathol. 1998 Jul;88(1):35-45.
17. Bedelbaeva K, Gourevitch D, Clark L, et al. The MRL mouse heart healing response shows donor dominance in allogeneic fetal liver chimeric mice. Cloning Stem Cells. 2004;6(4):352-63.
18. Leferovich JM, Bedelbaeva K, Samulewicz S, et al. Heart regeneration in adult MRL mice. Proc Natl Acad Sci USA. 2001 Aug 14;98(17):9830-5.
19. Heber-Katz E, Leferovich J, Bedelbaeva K, Gourevitch D, Clark L. The scarless heart and the MRL mouse. Philos Trans R Soc Lond B Biol Sci. 2004 May 29;359(1445):785-93.
20. McBrearty BA, Clark LD, Zhang XM, Blankenhorn EP, Heber-Katz E. Genetic analysis of a mammalian wound-healing trait. Proc Natl Acad Sci USA. 1998 Sep 29;95(20):11792-7.
21. Heber-Katz E, Chen P, Clark L, et al. Regeneration in MRL mice: further genetic loci controlling the ear hole closure trait using MRL and M.m. Castaneus mice. Wound Repair Regen. 2004 May;12(3):384-92.
22. Hampton DW, Seitz A, Chen P, Heber-Katz E, Fawcett JW. Altered CNS response to injury in the MRL/MpJ mouse. Neuroscience. 2004;127(4):821-32.

New Artificial Muscles Are Powerhouses

New Designs Are More Than 100 Times Stronger Than Natural Muscle

By Miranda Hitti WebMD Medical News

Reviewed By Louise Chang, MD on Thursday, March 16, 2006

March 16, 2006 -- The latest artificial muscles make natural muscles look like weaklings, according to a study in Science.
Researchers invented two types of artificial muscles that use high-energy chemical fuels -- such as methanol and hydrogen -- instead of batteries. The inventions can outwork natural muscles, with one design showing 100 times the strength of natural muscles.
The scientists included Von Howard Ebron, PhD, and Ray Baughman, PhD. Both work at the University of Texas at Dallas.
The invention should lead to powerful devices that truly "keep on going," states a journal editorial. But the new muscles don't yet give the "exquisite control" needed for tasks like catching and throwing balls, the editorial also notes.
Unplugging Artificial Muscles
Artificial muscles and electrical motors in robots and prosthetic limbs "are typically battery powered, which severely restricts the duration of their performance and can necessitate long inactivity during battery recharge," write Ebron and colleagues.
"Because of high electrical power needs, some of the most athletically capable robots cannot freely prance around because they are wired to a stationary power source," the scientists add.
Their artificial muscles work differently, tapping chemical energy in fuels instead of relying on batteries. One model converts chemical energy in fuels to electrical energy for movement or storage. The other model mixes fuel and oxygen to create heat for energy.
The latter version is "especially easy to deploy in robotic devices," Baughman says in a news release. "Students and scientists of all ages will be working on optimizing and deploying our artificial muscles," he predicts.
"The approach is not without challenges, but it could transform the way complex mechanical systems are built," writes editorialist John D. Madden, PhD. Madden works at Canada's University of British Columbia in Vancouver. Developing fine control over such artificial muscles is one of those challenges, Madden notes.

Nanotechnology May Repair Damaged Brains

TUESDAY, March 14 (HealthDay News) -- Rodents blinded by brain damage had their vision partially restored within weeks after being treated with nanotechnology developed by bioengineers and neuroscientists at the Massachusetts Institute of Technology.
The findings provide evidence that similar strategies might someday work in humans.
"If we can reconnect parts of the brain that were disconnected by stroke, then we may be able to restore speech to an individual who is able to understand what is said but has lost the ability to speak," study co-author Rutledge G. Ellis-Behnke, research scientist in MIT's department of brain and cognitive sciences, said in a prepared statement.
This method uses an extremely tiny biodegradable scaffold that provides brain cells with a place to re-grow -- like a vine on a trellis -- in the damaged area of the brain. This is the first study to use nanotechnology to repair and heal the brain and restore function in a damaged brain region. The approach may one day help treat stroke patients and people with spinal cord and traumatic brain injuries.
The findings appear online this week in the journal Proceedings of the National Academy of Sciences.
The study included young and adult hamsters with severed neural pathways. The animals were injected with a solution containing certain kinds of peptides (protein fragments) that create a mesh or scaffold of tiny, interwoven fibers. Brain cells are able to grow on this mesh.
Within about six weeks, the hamsters had regained useful vision and the adults' brains responded as well as the younger animals' brains.
"This is not about restoring 100 percent of damaged brain cells, but 20 percent or even less may be enough to restore function, and that is our goal," Ellis-Behnke said.
More information
The Brain Injury Association of America has more about types of brain injury.
Copyright © 2006 HealthDay. All rights reserved.

The Guru of Anti-Aging

MARCH 20, 2006

COVER STORY

Online Extra: The Guru of Anti-Aging

There's plenty doctors can do to control the effects of old age, says a leading light in the anti-aging medical movement

Since 1981, Dr. Ronald M. Klatz has served as the chief champion of anti-aging medicine. He coined the very term "anti-aging." In 1992, he became the founder and president of the American Academy of Anti-Aging Medicine, which he describes in his Internet bio as a "medical organization dedicated to the advancement of technology to detect, prevent, and treat aging-related disease and to promote research into methods to retard and optimize the human aging process." He isn't shy about expressing his support for the entire anti-aging arsenal of tools, including controversial drugs such as human growth hormone (HGH). He's even written books on the topic, including Grow Young with HGH, Ten Weeks to a Younger You, and Hormones of Youth.

During a telephone interview with BusinessWeek Science Editor Arlene Weintraub, Klatz discussed the history of anti-aging medicine, the controversies that have followed its success, and his hopes for the future of this nascent field. Following are edited excerpts from their conversation.

What inspired you to get into anti-aging medicine?
The goal of medicine is to prolong life. That's what most of us doctors go into medicine to accomplish. One day I looked in the mirror, and I saw wrinkles. I said, "Physician, heal thyself." Until the 1980s, scientists didn't have a clue as to how or why we age. Then it became very clear that medicine was developing new technologies for dealing with genetic disorders and chronic degenerative diseases. Many of these diseases occur in the aged. I felt that if medicine could control the metabolic effects of aging, we could control aging itself.

There's been a bit of controversy about the use of HGH, which was originally approved to promote growth in short children and to treat just a handful of diseases in adults. What is the role of HGH in the context of the entire anti-aging arsenal?
HGH is the most extreme example in anti-aging medicine. About 10% of patients who are on the full regimen are taking HGH.

Do you believe HGH reverses aging?
This is a matter of semantics. It does reverse bone loss, muscle loss, and it improves hydration of tissue. We're reversing the physical processes of aging.

What's your response to critics who say HGH isn't safe for otherwise healthy adults?
When they say it's not safe, it's as if they're screaming "fire" in a crowded theater. There will still be critics who beat their chests and come up with bogus research saying there are side effects. Those only occur when someone's taking massive amounts. In adults we're merely replacing the hormone to the normal level of a 30-year-old. That's just one-third to one-seventh of the dose that's been shown to be safe in children. This drug has been used clinically over the last 20 years in hundreds of thousands of young people and tens of thousands of adults. There is no published literature showing that HGH has caused any permanent side effects, or death. It's one of the best-researched drugs out there. The critics shouldn't make [danger] proclamations without a scientific basis. Show me the studies that say these treatments cause cancer or diabetes.

What else helps reverse the ravages of age?
There's no single "age reversal" drug, but we have a lot of things that work. Exercise, for example, can change the biomarkers of aging. If you use testosterone or estrogen, it might help maintain the health of the cells in your body. That can improve the biomarkers of aging. Aging is not one global thing. We haven't yet found a single control switch.

How quickly is the field of anti-aging medicine growing?
AAM has grown from 12 physician members to 17,500 in 85 countries. We'll have 26 seminars in 2006, where we'll train 30,000 doctors worldwide. With 1,500 physicians certified in anti-aging medicine, we think it's the fastest-growing medical certification program in history.

What's your ultimate hope for how the public might someday view anti-aging medicine?
I believe that one day it will be considered malpractice for any physician not to do what anti-aging physicians do today.

Copyright 2000- 2006 by The McGraw-Hill Companies Inc.
All rights reserved.

Cochlear Implants Aim for Age-Related Loss

We're working on being able to replace the body piece by piece.  We have eyes, and ears (now with hybrid implants), and we're working on being able to replace organs with 3 dimensional structures.  We've been able to replace limbs for some time, although they have been relatively crude until recently.  I don't think it will be long before the only thing left will be the brain.

---

By LAURAN NEERGAARD, AP Medical WriterMon Mar 13, 6:01 PM ET

Cochlear implants may not be just for the profoundly deaf anymore: Iowa scientists are developing the next generation, a "hybrid implant" to combine the best of bionics with regular hearing aids for age-related hearing loss.

If it works — and early study results are promising — it one day may help thousands of older Americans whose hearing is progressively fading. The key difference: Unlike regular cochlear implants, the hybrid model would let people keep their natural music appreciation even as it helps them hear speech more clearly again.

That's what attracted attorney Gordon Gross, a concert lover, to the experimental device five months ago. With his hearing aids at full blast, Gross could conduct one-on-one conversations. But he could barely distinguish sentences from the background noise during the meetings required for his job.

"Most people in my situation smile a lot, fake what they hear," says Gross, 74, of Buffalo, N.Y.

He's still undergoing required training to learn to recognize speech with the implant. But Gross recently popped in a "Phantom of the Opera" CD and noticed that, "where before I wouldn't understand virtually anything, I'm now beginning to pick up words and phrases. It is very exciting."

How does it work? Like tuning a piano, says Dr. Bruce Gantz, an otolaryngologist at the University of Iowa who invented the hybrid model now being tested at 26 medical centers around the country.

Normally, microscopic hair cells in the cochlea, the snail-shaped inner ear, pick up vibrations and convert them into electrical impulses that the brain recognizes as different sounds. Hairs in the deepest part of the cochlea pick up low-frequency sounds, such as music. Hairs at the cochlea's entrance pick up high-frequency sounds, including speech.

With age-related hearing loss, people tend to first lose high-frequency hearing. Initially, specific consonants disappear — they no longer can discriminate, say, a "c" from a "t." They stumble over more and more words until they're unable to decipher entire sentences, especially when there's competing noise. Hearing aids turn up the volume for all sounds, not just speech, and thus eventually quit helping.

"If you filter those (consonants) out to a great extent, you can make the sound as loud as you like and it's still incomprehensible," explains Dr. James Battey, who directs the National Institutes of Health's hearing-loss division.

Enter cochlear implants. Surgically placed behind and in the ear, the implant itself turns sound into electrical impulses that directly activate the hearing nerve, allowing the deaf to hear. They've proven particularly beneficial for deaf babies and young children, dramatically improving their ability to learn to speak and comprehend language normally.

But for people who aren't completely deaf, cochlear implants have a big catch: Snaking the electrode deep into the cochlea destroys whatever hair cells still live in the inner ear. If your only problem is detecting high-frequency sounds, a regular cochlear implant would destroy your ability to hear low-frequency sounds normally, such as music or the pitch that distinguishes one speaker from another.

Gantz's solution: Make the electrode shorter, so it only substitutes for the hearing that's already lost. Pair it with a regular hearing aid to amplify their remaining low-frequency hearing, and people just might hear again more like they did years earlier.

So far, about 60 patients have received the hybrid implant, manufactured by Cochlear Americas. About 10 have had it for more than a year. On standard hearing tests, those patients understand 70 percent of words a year after the implant — up from 25 percent before the surgery, Gantz says. That comprehension seems to continue improving as the brain rewires itself to better recognize the electronic signals.

More research is needed before the company seeks Food and Drug Administration approval. But NIH, which is partly funding Gantz's work, and independent specialists call the hybrid implant a potentially important step.

"It addresses patients who are in a very difficult middle ground," says Dr. John Niparko of Johns Hopkins University. "It allows them to perceive the richness of sound through the cochlear zones that are still working," while compensating for the "dead zones."

The brain does have to adjust to decoding electronically generated sound. Users require training, and some describe an echo effect for a few weeks. "It was almost as if I was hearing from two different places," recalls Paula Fuller, 61, of Haver Hill, Iowa.

But within a month of her January 2000 implant, she was hearing sounds she hadn't heard in years — birds chirping, the dialogue in a movie — and no longer avoiding social situations for fear she couldn't converse.