Parkinson's disease Updates for Cogane, Neupro Patch, Droxidopa, Lu 02-750, and Azilect

In the news and demonstrating the need for a PD pipeline fast track through the FDA

As of 12/09/2009 Phytopharm has raised the money needed to bring Cogane to Phase II trial in the first half of 2010.  The results for the Phase II trial of Cogane, the neurotropic factor which uses both GDNF and BDNF to cross the blood brain barrier, are expected in 2012.

Another announcement is that Cogane will be tested for Huntington's Disease.

Phytopharm stock is doing well.

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For all awaiting the return of the Neupro Transdermal Patch, here's the latest news from UCB, the global biopharma. After the crystalization recall and subsequent removal from both the European and the US market, many patients who had found relief from this unique molecule which helped patients improve against a broad range of day-night symptoms by maintaining a constant plasma level to relieve motor symptoms, sleep problems and morning akinesia (limited motion) were with only enough supply to titrate down.

The patch was approved by the EMEA (the European Medicines Agency) for approval to return to the European market by the summer of 2009 and there are 33,000 PD and RLS patients who are using it in Europe; however, the Neupro rotigotine patch is still not available in the US.

A year ago in December 2008, UCB submitted their response letter to the FDA. 

In June of 2009 am extensive update on the cold chain data was submitted to the FDA.

The dialogue continues and it is expected that Neupro will be made available to US patients in 2010 according to UCB.

We've supplied a link to one online pharmacy which will fill a prescription request and other readers have supplied links to others in the comments sections of previous posts.  If you're looking for the Neupro patch, check these posts and their comments sections.

June 2010 Neupro Patch Update:
With the blessing of the FDA, UCB has gone back to the drawing board with the Neupro patch to eliminate the need for cold storage.  The implication of this announcement suggests that it could be as long as 3 years before the patch can be returned to the USA market.

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In the research and the pipeline are other GDNF delivery options. One approach is biodegradable microspheres still in research.  Another is an intranasal delivery in research now studying nasal toxicity and the quantity of the GDNF which reaches the brain.  Ths latter study is still in lab rat mode before moving on to human trials.

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The mixed bag news is that there is motivation to develop new therapies which work better than older, existing therapies. That's good.  In Europe alone, PD accounted for a $1 billion market which is expected to grow to about $2.25 billion by 2015.  Even if a cure is found, there is a growing number of people developing Parkinson's disease as the world population continues to expand and as diagnoses become more accurate (another market in itself) and are done at an earlier stage of the disease...

We'd love to be able to tell you more about a unique dopaminergic agonist being developed but Lu 02-750 is very hush-hush.

In October of 2009 Lundbeck announced the beginning of Phase I clinical trials for Lu 02-750 in a Press release. They anticipate regulatory filing probably after 2011.

Lundbeck is a global pharmaceutical company specializing in brain disorders.  Although headquartered in Copenhagen, Denmark H Lundback A/S has employees worldwide through company acquisitions and development partners.

 

Lundbeck is also developing treatments for AD, Schizophrenia, Freidreich's Ataxia, Major depressive disorder. They also market medications for insomnia.

On an interesting note, Lundbeck is one of the few pharmaceutical companies listing non-medication treatments for Parkinson's disease. 

The development of Lu 02-750 was apparently conducted under the direction of Professor Håkan Wikström who describes himself as a bio-professional geek. Professor Wilkstorm, is on the faculty of Groningen University in the Netherlands and is a co-founder Axon Biochemicals B.V.

About Lu 20-750 it has been reported that "In animal studies, (it is) the drug candidate shown to have a stronger effect on the disease than current drugs."
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News from Parkinsons Action Network about Health Care legislation affecting Parkinson's disease

First, on Saturday, December 19, the Senate gave final approval to the Department of Defense Appropriations bill, sending to President Obama a piece of legislation including $25 million for the innovative Neurotoxin Exposure Treatment Parkinson's Research (NETPR) program.

The NETPR program is the only Parkinson's-specific research program funded by the Federal government.  Advocates must work to secure funding for this program every year, and the Parkinson's community rallied through a tough economy to ensure that the NETPR program did not receive a budget cut.

The second piece of legislation also took place on Saturday when the Cures Acceleration Network (CAN) Act of 2009, introduced by Senator Arlen Specter (D-PA), was included in the final Senate version of health care reform legislation.  The CAN Act seeks to cut the time between discovery and development of new drugs and therapies.  For some time PAN has focused on this troubling trend. Thanks to Sen. Specter's leadership and PAN advocates who contacted their Senators, a focus has been placed on accelerating tomorrow's therapies and drugs through the development pipeline. 

The Senate expects to vote for final approval of the bill before Christmas, and PAN will work to sustain the CAN amendment during the Conference between the House and Senate.
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As of December 14, 2009 Azilect no longer carries the cheese effect warning.
You can read about in the Teva Pharmaceutical Industries Ltd press release
If you haven't read Dr Karl Kieburts comments about the ADAGIO study and the inconclusive results of the 2mg dosage as opposed to the positive results at 1mg, please take a look:

Link to the ADAGIO Study commentary by Karl Kieburtz, MD, MPH
There will probably be another differently drawn Azilect (rasagiline) study of the 2mg dose.
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June 2010 COGANE Update
Phytopharm PLC received a USA regulatory approval by the FDA to begin the Phase II Clinical Trial.
Patient enrollment should begin in late 2010
You can read the Phytopharm press release here
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Droxidopa from Chelsea Therapeutics International (Nasdaq: CHTP)  Droxidopa is described as a pro-drug to treat neurogenic orthostatic hypotension (NOH)

"Droxidopa provided statistical significance in the treatment of Neurogenic Orthostatic Hypotension (NOH) improving the motility of these patients and reduced their risk of falls with a benign safety profile. These improvements were measured through an orthostatic hypotension questionnaire and corresponding clinical indications"

• NOH is a drop in blood pressure resulting from deficient release of norepinephrine and is characterized by dizziness, weakness, blurred vision and fatigue.
• NOH occurs in patients suffering from autonomic dysfunction and movement disorders such as Parkinson's disease, multiple system atrophy and pure autonomic failure.
• Droxidopa is a synthetic catecholamine that is directly converted to norepinephrine (NE) via decarboxylation, resulting in increased levels of NE in the nervous system, both centrally and peripherally.

In December 2009, a press release announced that a small subgroup analysis of 44 PD patients (all on L-dopa) and enrolled in Study 302, a Phase III withdrawal study, demonstrated a "more robust response compared to the overall population study." 
"Study 302 evaluated the efficacy and safety of Droxidopa, a pro-drug that results in increased body stores of norepinephrine, in 101 patients with symptomatic NOH. All patients in Study 302 were evaluated for functional and symptomatic improvement through multiple endpoints including the orthostatic hypotension questionnaire (OHQ)."

Although Droxidopa is currently on the market in Japan, it is not on the general market in the US.  In 2007 Droxidopa was awarded orphan drug status specifically to treat NOH in the US and in Europe. "for the treatment of symptomatic NOH in patients with primary autonomic failure (Parkinson’s disease, multiple system atrophy, and pure autonomic failure), dopamine-ß-hydroxylase deficiency, or nondiabetic autonomic neuropathy"

The Future of Isradipine and Parkinson's Disease

Can Isradipine reverse neuronal degeneration in Parkinson's?
Parkinson's is a common neurological disease, affecting over 1.5 million people in the USA alone. The risk of PD increases as we get older, especially after we pass sixty. PD progression is the result of the damage and on-going deterioration of the dopamine neurons.

Because dopamine is a chemical messenger for the brain, the death of its neurons causes an ever increasing slow loss of motor control as it causes the typical PD symptoms: tremor, balance, loss of sense of smell, stiffness, inability to dress one's self, swallowing and speaking problems, sleeping issues, sexual dysfunction, dystonia, depression, apathy and many others.

There is a great deal of research underway but there is no cure. The only drug that has some proven neuro-protection thus far is Azilect.

Researchers understand that the neurons die but not much about how or why. While there are signs of the disease process in many regions of the brain, the core symptoms of PD occur when the dopamine neurons in an area of the brain called the substantia nigra pars compacta are damaged. Although in their youthful stage they relied upon sodium channels, as these neurons age they rely on calcuim channels to maintain autonomous activity. This reliance puts the metabolic mitocondria under sustained stress causing cell aging and death.

The calcium channels underlying the autonomous activity of the dopamine neurons are similar to the L-type channels of the heart and smooth muscles. Systemic administration of Isradipine, an L-type blocker of C type channels (Ca2+) causes a reversion to a sodium mechanism to produce independent activity.

Reversion to the sodium and HCN channels found in the juvenile substantia nigra offers protection from toxins to lab rodents with experimental PD. In a few years this could result in a Parkinson's Disease neuroprotective usage for a drug class that has been safely used by cardiac patients for decades. There is the possibility that reversing the synaptic dysfunction, neuron degeneration and reduced plasticity can restore brain cellular and molecular homeostasis; a return to normalcy.

Now there is a fresh approach to combating this disease, a different viewpoint. Isradipine Phase II clinical trials for safety and efficacy begin May 2009.

This research also suggests that although genetic and environmental factors can hasten its onset, PD is programed into all humans, if we live long enough we may all get it.

Resources:

10/06/2007
Calcium, aging and neuronal vulnerabilty in Parkinson's Disease
PUB MED NIH
D. J. Surmeier

07/05/07
Parkinson's disease: return of an old prime suspect
PUB MED NIH
D Sulzer, Y Schmitz

06/06/07
Calcium and Neurodegeneration
PUB MED NIH
MP Mattson

06/28/07
"Rejuvenation" protects neurons in mouse models of Parkinson's disease
PUB MED NIH
CS Chan, JN Guzman, E Ilijic, JN Mercer, C Rick, R Tkatch, GE Meredith, DJ Surmeier

HAPPY NEW YEAR

I've been diagnosed PD for 5 years now. It seems to be the tremor dominant variety of the disease, although an aunt also had PD, my Great Grandfather had a neurological disease then called senility and lastly my mother has something now being called old age previously called Alzheimer's disease. So it could just be that I have genetic PD with an exposure to pesticides in my childhood and again as a young adult (gun-trigger.)

My PD started out with loss of sense of smell and foot dragging, as well as a discrete tingling pain in my body and arms. After a year or two I started having a left arm tremor when I felt emotional: either good, bad or stress. Some times in a very stressful situation my arm would shake a lot but mostly it is a very gentle hardly noticeable hand tremor.

Before I was DXed I was pretty sure what I had so I started taking COQ10 450mg/day. After I was DXed, my neurologist had me increase the COQ10 to 1200mg/day. He also added Amantadine 200 mg/day. Eventually he had me add Mirapex and Selegiline. At this point I started having very complicated hallucination's and vivid dreams. I didn't get obsessed over gambling like many PD patients but I started thinking about women obsessively.

Meanwhile I experienced several symptoms that were new to me, double vision, swallowing difficulty , occasional difficultly speaking,stiffness in my left arm and greater rigidity in my whole body. About a year ago I started using a cane because of the pain my arthritis was causing when I walked.

After my neurologist moved away my Kaiser health plan sent me to another neurologist who told me the hallucinations I was experiencing weren't too bad and that I should "learn to live with them." He thought it was a trade-off worth trying. (Easy for him to say!) When I refused to go along with that he had his assistant try to convince me that Levodopa was my only other good alternative. I changed neurologists again and was prescribed Azilect 1 mg/day and added Dynacirc 10mg/day.

That was about 1 1/2 years ago. Since then I have added Turmeric 1200mg/day for my PD and osteoarthritis. Turmeric is a powerful herbal anti-inflammatory whose main component is curcumin, the significant ingredient. I also began taking Glutathione with NAC (N-Acetyl-L-Cysteine) as a sub lingual 450mg/day accompanied by Milk Thistle Extract.

My present condition is pretty decent considering. Biggest problems are sleeping, stiffness and rigidity, pain in left knee, cane dependency, depression and having a feeling of foreboding about the future.

As we go into the new year I plan to try to eliminate these problems by tyring new approaches or continuing ones that have helped. Massage therapy has helped reduce my stiffness very much, as has aqua therapy. I've started using the Nautlis machines at the aqua center and I will continue that in the new year. Massage with aqua therapy has been making my knee less painful, so I've started to wean myself from the cane.

You may have noticed I haven't called any of these things New Year's resolutions. I don't have a good track record in that department...check with me in a month.

A Good New Year to All,
Stephen

Massage Therapy and PD

Keeping my Parkinson's disease progression as slow as possible


I've had Parkinson's disease for 5+ years now. I've been trying to avoid taking levodopa because of its possible side effects that often start after 5 years of increasing dosage. Medications I now take are azilect, COQ10, and isradipine for PD. They eliminate or reduce my symptoms of tremor, soft voice and foot drop, while leaving me with slowly progressing muscular rigidity, gait difficulty and slowness of movement.

Seven months ago I began massage therapy for arthritis in my knees because I had read about positive results in a Yale University study for the CDC. The study showed that Swedish massage therapy reduced pain while improving flexibility and range of motion in arthritis patients.

I've been getting a one hour massage every week and the pain in my knees is mostly gone, unless I lift heavy things or wear shoes that are not soft, flexible and low heeled. In recent months I've been wearing Dr Scholl's Lara medium or wide width with the gel insole. Yes, I am gellin' and it seems to help my comfort level.

Most large metro areas will have lots of Massage Therapists. Find one who is familiar with Arthritis and Parkinson's and is listed by the American Massage Therapy Association. Most will offer several different styles of massage. Each of us is different, but Swedish massage has tested as pain relieving for arthritis.

In a small study conducted by Touch Research Institute at the University of Miami 16 adults diagnosed with Parkinson's disease were randomly assigned to either progressive muscle relaxation exercise or massage for 30 minutes twice a week.

The results were that those in the massage group had improvements in daily functioning and urine tests showed a reduction in stress hormone norepinephrine and the massage group had fewer sleep disturbances.

I will discuss my own massage therapy in more detail in an upcoming Parkinson's Focus Today post.

Azilect First Drug To Slow Progression

The Parkinson Disease Foundation issued a statement on June 16, 2008 saying that Teva Pharmaceuticals has applied for permission from the FDA to relabel Azilect (rasagiline) for its potential to slow the course of the disease.
According to Teva they have new data from an 18 month study called ADAGIO that suports a neuroprotective benefit. This data has not been released yet by Teva although it is said to have passed its Phase III studies(trials.)
Azilect is already approved for symptom easing and is widely used for that purpose.
If the FDA approve’s Teva’s request, this would be the 1st PD drug to be marketed as :”disease slowing.”
Teva Pharmaceuticals is an Israeli company which trades as TEVA on NASAQ and as MYL on NYSE.

Addendum 2010
The ADAGIO study has been completed although there will probably be another 2mg study may be in the works with different parameters.  You can read the commentary by Dr Karl Kieburtz about the reasons for the inconclusive aspects of the study in regards to the 2mg dosage...as opposed to the 1mg part of the study. These remarks were published at the MJFF website.

Link to the ADAGIO Study commentary by Karl Kieburtz, MD, MPH  

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