Neuropathy Drug Research fails!

One of the much-trumpeted and supposedly most promising, gene therapy treatments, for neuropathic problems, called SB-509, has been abandoned by the company involved. It's some consolation that they're now concentrating solely on HIV therapies. The company involved, (Sangam) has suffered a significant drop in its share value but for us, it's just too depressing. Hopefully other companies will continue, or resume the search for an effective treatment for neuropathy. Link to article below.

Sangamo Fails Diabetic Neuropathy Study, Falls Back on HIV, Other Programs
by Luke Timmerman 10/3/11

Sangamo Biosciences’ lead drug candidate has flunked its biggest test yet in clinical trials, and the company said this morning that it’s time to move on to other programs.

The Richmond, CA-based company (NASDAQ: SGMO) said today that SB-509 failed in a study of 170 patients that randomly assigned patients with diabetic neuropathy to a new drug or a placebo. The company has now decided to scrap development of this particular drug, and will put more emphasis on its experimental treatments for HIV and single gene disorders.

Shares of Sangamo fell 22 percent to $3.38 shortly after the opening of trading this morning.

There wasn’t any sugarcoating of the results. Sangamo’s drug missed its primary and secondary goals, in which it was seeking to help diabetes patients fight one of the most common complications of the disease—numbness and tingling of nerves in the extremities. “We are disappointed,” said Edward Lanphier, Sangamo’s president and CEO, in a statement.

Sangamo’s study has been watched by scientists because of its potential for treating disease in a new way, through its zinc-finger protein technology. The technology is used to turn specific genes on or off in all kinds of living organisms, and one of the obvious applications is to turn off disease related genes in humans. Sangamo has shown some interesting results recently with a new treatment against HIV, and for a certain kind of hemophilia, but both programs are at earlier stages of development. Sangamo, which went public in 2000, has no drugs of its own on the market.

http://www.xconomy.com/san-francisco/2011/10/03/sangamo-fails-diabetic-neuropathy-study-falls-back-on-hiv-other-programs/

Whats New On The Neuropathy Research Front Webinar Vid

Today's YouTube video is full of lots of useful information from a recent Neuropathy Association webinar. Unfortunately, the sound is somewhat disembodied and often sounds like those irritating, computer-generated voices but the content is valuable and worth looking at and listening to if you have a free half hour. Be warned, it can be somewhat technical but the slides do help explain the text.

"What New Neuropathy Research Can We Be Hopeful For?" - 2014 Webinar
Published on 17 Jul 2014




https://www.youtube.com/watch?v=wBbK5oKWHzA#t=169

Zebra Fish The New Rats In Nerve Damage Research

Today's fascinating post from medicaldaily.com (see link below) looks at how zebra fish are being used to study how nerve damage progresses with certain neurological diseases (eg neuropathy). The fact that these fish have an 82% likeness with humans in terms of proteins means that results of studies are less likely to be misleading than those involving other research animals. We've heard of various sea creatures being used to study human neurology and developing nerve damage treatments before but apparently studying myelin sheath degradation in Zebra fish brings up many close comparisons with the same cause of nerve damage in humans but how did they ever discover that in the first place!!

Zebrafish, 82% Similar To Humans, Reveal New Insights On Neurological Disorders And Treatments
By Anoopa Singh | Jun 26, 2013

Zebrafish reveal much about neurological disorders and how to treat them.

Neurological disorders in humans are often difficult to study in human brains. As a result, animal models need to be used to simulate the workings of the human nervous system. Usually, scientists will rely on mice, but recently, the use of zebrafish has become popular due to the animal's utility.

Charcot—Marie—Tooth disease (CMT) is causes by a hereditary genetic disorder that affects the nerves that branch throughout the body in young adults. The disease leads to nerve damage and causes a weakness of muscles, foot and hand deformity, loss of muscle mass, and numbness in the lower body. CMT eventually leads to disability and a loss in sensation in the places most affected.

A new study using zebrafish, done by Andrew Grierson, Ph.D., of University of Sheffield, has revealed a great deal about CMT and potential therapies. Humans and zebrafish have proteins that are 82 percent alike — this is important because it indicates that zebrafish are suitable in studies that compare results to potential treatments for diseases in humans. When researchers altered the genes of zebrafish to be the same as patients of CMT, similar symptoms were seen as the fish aged. Once they matured into adulthood, the fish lost the ability to swim properly. The scientists feel that the difficulties in swimming can be paralleled to the difficulties humans face in walking after CMT has fully developed.

Using the zebrafish, researchers were able to identify what goes wrong in neurons as a result of CMT for the first time. They saw that the myelin sheaths around neurons began to degrade. Similarly, the far branches of nerve cells also started to degrade, leading to the sensations of pain, as messages like sensation could not travel up and down this part of the neuron anymore. Both of these issues led to the pain and neurodegeneration suffered by CMT patients.

The researchers have said that all of this would not have been clear in any other animal. In other animals, the disease starts its effects very early in development, but in humans, disease onset is usually in adolescence. This difference in other animals skews results and makes findings inconsistent with the disease's effects in humans. Grierson said, "Using zebrafish we were able to develop a model with an adult onset, progressive phenotype with predominant symptoms of motor dysfunction similar to [what happens in humans]."

He added that while we know much about other neurodegenerative diseases, others seem to escape our grasp. "Motor neurons are the largest cells in our bodies, and as such they are highly dependent on a cellular transport system to deliver molecules through the long nerve cell processes which connect the spinal cord to our muscles," he continued. "We already know that defects in the cellular transport system occur early in the development of diseases such as Alzheimer's disease, Motor Neuron Disease and spastic paraplegia. Using our zebrafish model we have found that similar defects in transport are also a key part of the disease process in CMT

Now that so much has been found out about the way CMT changes neurons for the worst, researchers can start to develop targeted therapies and treatments for the disease. There is currently no cure for CMT, nor are there any drugs that can help manage its symptoms. Patients often depend on physical or occupational therapies or surgeries for relief from symptoms.
 
While a cure may not be made tomorrow, the prospect of it and improved disease management therapies now exist.

Source: Chapman AL, Bennett EJ, Ramesh T, De Vos KJ, Grierson AJ. Axonal Transport Defects in a Mitofusin 2 Loss of Function Model of Charcot-Marie-Tooth Disease in Zebrafish. PLOS ONE. 2013.

http://www.medicaldaily.com/zebrafish-82-similar-humans-reveal-new-insights-neurological-disorders-and-treatments-247168#92xi6cLxdeJUUlFI.99

Research into Neuropathic Pain Products

Today's post comes from WWMR, Inc. which is an established marketing research and strategic consulting firm (see link below). They have looked at current progress amongst the pharmaceutical companies, concerning drugs to treat neuropathy. We have to be pleased that the report sees new drug treatments from various companies in the pipeline and looking at the proposed financial benefits, indicates that both the market is growing and there are profits to be made. We'll have to wait and see but it does seem that the general trend is to refine current treatments rather than come up with something totally new. That may well be because the transmission of pain signals at chemical and biological level has long been recognised and is more or less indisputable and that's why the anti-depressants and anti-convulsants have been used in the first place. Talking about calcium and sodium channels and norepinephrine and serotonin reuptake inhibitors, is very difficult to understand unless you're a scientist, so we have to trust that they're going in the right direction. One thing seems to be clear and that is that the chemists and biologists from the major drug companies are now seriously looking at how neuropathic pain works and how to treat it. Let's hope that they come up with solutions that the bosses will see as profitable in these days of financial crisis and that they won't be delayed by national medical authorities, otherwise we'll be back to square one. A lot of 'ifs' and 'buts' ahead then but at least there are signs of progress!

Neuropathic Pain Products in Europe Grow to US$1.7 Billion by 2012
Troy Franey,WWMR, Inc.

SAN FRANCISCO, December 16 /PRNewswire/ -- By 2012, the market for drug treatment of major neuropathic pain conditions in the five major European pharmaceutical markets -- France, Germany, Italy, Spain and the UK -- will reach US$1.7 billion. Given this substantial commercial potential and a patient population approaching 2 million in Europe alone, upcoming products for the treatment of Neuropathic Back Pain, Diabetic Neuropathy, Post-Herpetic Neuralgia, Trigeminal Neuralgia, and HIV / AIDS Neuropathy are vigorously being research and developed by pharmaceutical companies.

The European neuropathic pain market is characterised by a particularly high level of unmet need for effective therapeutics due to the under- utilisation of anti-depressants, the lack of opioid availability, commonly used to treat neuropathic pain in the U.S. and certain European country- markets, but not others. This under-utilisation stems primarily from a lack of awareness about the potential utility of these drugs in neuropathic pain treatment and concerns about opioid addiction.

The anticonvulsant Neurontin (gabapentin) has recently experienced significant uptake in some countries in Europe, demonstrating the magnitude of the potential for other drugs with newer mechanisms of action. Now the product is facing generic competition in Europe, and with Pfizer's recent NDA submission to the US FDA for the follow-on drug pregabalin, renewed attention is being focused on anticipated changes in the neuropathic pain market.

At least 41 agents, triple the number from 1999, are in active clinical trials for the treatment of neuropathic pain worldwide. Late-phase products in clinical development for neuropathic pain include calcium channel antagonists pregabalin (Pfizer) and ziconotide (Elan Pharmaceuticals); sodium channel antagonists topiramate (J&J / Ortho-McNeil Pharmaceutical), mexiletine (Boehringer Ingelheim), and oxcarbazepine (Novartis / Kissei); glutamate / NMDA antagonists memantine (Neurobiological Technologies / Merz) and lamotrigine (GlaxoSmithKline / Bristol-Myers Squibb); cyclo-oxygenase inhibitors meloxicam (Boehringer Ingelheim/ BMS / Abbott Laboratories) and lornoxicam (Roche / Nycomed Pharma); cannabinoid receptor agonist THC:CBD (GW Pharmaceuticals / Bayer AG); neuromuscular blocking agent botulinum toxin A (Allergan); norepinephrine and serotonin reuptake inhibitor duloxetine (Lilly / Quintiles / Shinogi); and alpha adrenoceptor agonist clonidine gel (Curatek Pharmaceuticals).

European Neuropathic Pain is a newly released report on the market potential for pharmaceuticals to treat neuropathic pain in the five major pharmaceutical markets in Europe -- France, Germany, Italy, Spain, and the United Kingdom.

Recent reports include:

-- Worldwide Peripheral Neuropathy
-- U.S. Neuropathic Pain
-- Brand Erosion by Generics
-- Rx Brand Erosion by OTC Switches
-- European Pharmaceutical Pricing and Reimbursement

WWMR, Inc., is an established marketing research and strategic consulting firm with global capabilities. Since 1994, WWMR has provided over 500 insightful, proprietary studies to pharmaceutical, biotech, medical device, and diagnostics companies worldwide. Using primary and secondary research methodologies, WWMR provides market and product assessments, competitive intelligence, forecast modelling, patient population projections, product launch monitoring (pre- and post-), primary marketing research and medical economic analyses.

Distributed by PR Newswire on behalf of WWMR, Inc.

http://www.prnewswire.co.uk/cgi/news/release?id=114075