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Long Views

Peering into the crystal ball

Sure we want long lives — but that’s not all.

We want to stay healthy and active so we can live those extra years to the fullest. Toward that end, eight Stanford experts give us some leads on what they consider the most promising medical advances to achieve long lives well-lived.


Frank Longo, MD, PhD, chair of neurology and neurological sciences, studies cellular signaling mechanisms that show promise as the basis of treatments for Alzheimer’s disease and other neurological disorders.
Greatest advance: One of the most exciting areas is the benefit of exercise for preventing cognitive decline. Studies show that a person who exercises four or five times per week can reduce the risk of developing dementia by as much as 50 percent. If we had a drug that reduced risk of dementia by 50 percent, we’d probably all be taking it, especially if the side effects were to prevent cardiovascular disease and hypertension, as they are for exercise.
Hottest in the pipeline: Development of drugs that target underlying mechanisms of Alzheimer’s. In 2000, we had essentially no such drugs in advanced clinical trials. But in 2007, we had roughly 20 treatments in advanced trials. That’s a huge step, and it’s happened because of the fantastic basic neuroscience done in the ’80s and ’90s that increased our understanding of the mechanisms behind cognitive loss. One of the most exciting treatments being tested uses antibodies to remove accumulations of amyloid protein from the brains of Alzheimer’s patients. It’s been very promising in animal studies and initial human trials.
Dream advance: To prevent dementia and cognitive loss. A protein called BDNF helps maintain healthy neurons and neural connections in our brains. BDNF levels decline during normal aging, and decline even more in Alzheimer’s patients. We’ve recently developed a small molecule that mimics the beneficial effects of BDNF and can be taken as a drug. Its effects have been very encouraging in mice.


Brian Wandell, PhD, psychology professor and visual neuroscientist, is co-founder of the Stanford Center for Image Systems Engineering. He studies visual processing in the brain and develops related technology applications, and was elected to the U.S. National Academy of Sciences in 2003.
Greatest advance: Lens and cornea replacement. These operations have been enormously important and successful. Cataracts used to cause blindness, but can now be removed in an outpatient procedure that restores high-quality vision.
Hottest in the pipeline: Next-generation lens replacement. We currently have limited ability to treat age-related macular degeneration, a disease that robs people of central vision and ability to read. But a new kind of artificial lens that acts like a telephoto system can restore some vision to people with the condition. One such device has just finished clinical trials and is awaiting FDA approval.
Dream advance: Retinal implants. Of course, the real dream would be to prevent eye diseases. But in the meantime, if a retina goes bad, it would be wonderful to be able to replace it with an electrical or chemical device that provides reasonable substitute vision. Replacing a retina is much more complicated than replacing a lens, since a retina is like a tiny computer that converts light into electrical impulses. But people are already working on these artificial retinas.

“Then suddenly Viagra came out, and I was amazed. I’d like to be amazed again.”

Male sexuality

Robert Kessler, MD, professor of urology, studies male erectile dysfunction and male infertility. A urologist for more than 25 years, he is a leader in the field of urologic prostheses and has demonstrated and taught the procedures at medical centers around the world.
Greatest advance: Oral medications for erectile dysfunction — Viagra, Levitra, Cialis. They all work by a similar mechanism, by blocking a molecule that can inhibit erections. These medications are effective for about half of those with erectile dysfunction. They do have side effects, however, and a small percentage of patients can’t tolerate them.
Hottest in the pipeline: Longer-lasting oral medications. Patients don’t like having to take a pill and then wait to have intercourse — they want to be more spontaneous. There is already a Cialis pill that lasts 36 to 48 hours, and researchers are working on longer-acting versions. The problem is that sometimes the side effects last that long, too.
Dream advance: A genetically engineered protein that you could inject into the penis to stimulate the growth of new blood vessels. It would increase blood flow to the penis and make it easier to get erections. You might need only one injection every two years, or even just once. This advance is probably still many years off — but before Viagra was developed, we thought an effective oral medication was years off. Then suddenly Viagra came out, and I was amazed. I’d like to be amazed again.

Female sexuality

Leah Millheiser, MD, instructor in obstetrics and gynecology, is the director of the Female Sexual Health Program at Stanford. She studies female sexual medicine and menopausal health.
Greatest advance: There are no FDA-approved medications for the treatment of female sexual dysfunction. However, purely identifying that female sexual dysfunction exists in the aging population has been a coup for my field. A recent study showed that women between the ages of 57 and 85 continue to be sexually active, but they also continue to have sexual complaints. We think that 50 percent of women older than 59 experience sexual dysfunction. And that’s largely been ignored.
Hottest in the pipeline: We have four medications on the horizon that may be FDA-approved in two to three years. Women would take them within 24 hours before having sex. One of them, Bremelanotide, is a nasal spray that acts on neurotransmitters to help treat low libido. Another medication, Alprostadil, is a topical lotion that increases vasodilation of the genitals, leading to greater lubrication and arousal. Many factors affect female sexuality — psychological, hormonal, neurological and circulatory — and the same medication won’t be right for everyone.
Dream advance: That every patient feel comfortable speaking to her doctor about sexuality, and that doctors become educated in the field of female sexuality so they know how to best serve their patients. Because medicine is not just about prescribing a medication, it’s knowing how to talk to the patient about it. Doctors aren’t taught this in medical school.


Sam Most, MD, FACS, chief of facial plastic and reconstructive surgery, has performed hundreds of facial aesthetic and reconstructive procedures. He has written numerous book chapters and articles on the subject and recently received the Ben Shuster Memorial Award for his research on facial nerve injury; he was also elected by his peers to the Best Doctors Inc. database of top specialists.
Greatest advance: More treatment options, both surgical and nonsurgical, including many noninvasive techniques with faster recovery time. In the last 10 years we’ve developed more injectable fillers, newer laser peels with two-day recoveries, and intense pulsed-light treatment to reduce pigmentation of the skin. We can better tailor treatment to the patient. We’ve also learned the importance of preventing skin damage by limiting exposure to sunlight, smoke and other harmful environments.
Hottest in the pipeline: The recognition that volume loss accounts for many of the facial features associated with aging. In other words, the face deflates as well as descends. Both bone and fat are lost. We’re developing new techniques to restore volume, such as fat transfers and implants on the bone. This will lead to a more natural, rejuvenated look and avoid the “stretched” look of bad plastic surgery.
Dream advance: A noninvasive technique for both lifting and volume enhancement that truly reverses the effects of aging three-dimensionally. Eventually we might use stem cells from the patients themselves to restore facial volume.


Stefan Heller, PhD, associate professor and head of the research division in otolaryngology, is looking for a biological cure for deafness. He studies how to coax stem cells to turn into new hair cells.
Greatest advance: The cochlear implant. Hearing is currently the only sense that can be restored with technical devices. The implant gets pushed into the cochlea and directly couples with the auditory nerve to transmit sound to the brain. Adults who have completely lost their hearing can’t be helped by a hearing aid, but as long as the auditory nerve is intact, the implant will restore hearing ability in many patients.
Hottest in the pipeline: The short cochlear implant. This variation on the cochlear implant restores only the high frequencies. It’s currently being tested in clinical trials. Since the high frequencies are lost first during aging, this would be a solution for some forms of age-related hearing loss, and an alternative for those who don’t want to wear a hearing aid.
Dream advance: My dream would be to see in my lifetime a drug that stimulates regeneration of cochlear hair cells. This would be a biological solution that would restore normal hearing and make implants and hearing aids obsolete.


Tom Andriacchi, PhD, a professor of both orthopedics and mechanical engineering, studies the biomechanics of human movement and examines how artificial joints, injuries and disease impact that movement.
Greatest advance: Joint replacement. It’s the most successful surgical procedure in terms of changing people’s lives that I know of. Osteoarthritis — the wearing out of joints — involves crippling pain and eventual joint fusion. It used to leave people in wheelchairs. Now, with new mechanical joints, those people stay mobile and active.
Hottest in the pipeline: Cartilage replacement. This means culturing cartilage cells in the lab and placing them in the joint to grow new cartilage. This would be a biological solution to joint replacement rather than a mechanical solution. The advantage of this is that, unlike mechanical parts that wear out with usage, biological replacements can actually get stronger with usage. It will be a few years before this is reality, but all the pieces are in place for it to happen.
Dream advance: Prevention. If you can catch degenerative conditions more quickly, you can do a lot to stop the disease from progressing, and surgery never becomes necessary. Ideally, in the future when you would go for your annual physical, you’d get an MRI and maybe a blood test that would detect whether your cartilage is starting to break down. Treatment could be started right away to prevent the condition from worsening. I’d also like to see more inventions that help decrease the daily stress on joints throughout the life span.

Bone health

Rachel Wagman, MD, clinical research director at the biotech company Amgen, studies osteoporosis and other metabolic bone diseases. She has been involved in the clinical development program for denosumab, a new product being studied for treatment of osteoporosis. She is also an adjunct clinical assistant professor of endocrinology at Stanford.
Greatest advance: Greater choice in treatments. An increased understanding of bone biology has allowed us to develop many new therapies that have become available in the last 12 years. We now have numerous drugs for slowing bone loss, which may be taken orally, intravenously or subcutaneously. We have the first approved drug for building new bone, teriparatide. All of this means a physician can tailor the therapy to the patient. It’s not a one-size-fits-all paradigm anymore.
Hottest in the pipeline: New drugs with greater efficacy and fewer side effects. Current medications reduce fracture risk by about 50 percent. We’d like to do better. Some of the most advanced drugs in development include drugs that inhibit bone resorption to slow bone loss, such as denosumab and cathepsin K inhibitors, and more drugs for building new bone, such as Dkk-1 and sclerostin inhibitors.
Dream advance: Better diagnosis and treatment of osteoporosis. A patient who has had a low-trauma fracture — for example, from a fall on the sidewalk — should be evaluated for osteoporosis. The number of estimated osteoporotic fractures in this country is about 1.5 million per year — more than the cases of cardiovascular disease, stroke and breast cancer combined. Yet often osteoporosis is not recognized or treated.






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