Wednesday, March 12, 2008

A hopeful future for Parkinson's disease patients

As discussed in our recent feature Parkinson's Disease Market analysis and forecasts Parkinson's disease is the second most common neurological disorder, affecting approximately 4.1m people worldwide.

Parkinson's disease is a neurodegenerative disorders characterized by the progressive loss of dopaminergic neurons and hence pharmacotherapy centers on bringing dopaminergic activity back to normal. The range of options open to Parkinson's disease patients is however changing.

Treatment of Parkinson's disease currently includes the use of levodopa, COMP inhibitors and dopamine agonists

Levodopa - the Gold Standard: Since its introduction in the 1960s, levodopa has been considered the gold standard drug therapy for Parkinson's disease. Levodopa is a precursor to dopamine that, when given to people with Parkinson's, is converted into dopamine by nerve cells in the brain. The increase in dopamine may reverse many of the disabling symptoms of Parkinson's disease.

Treatment with dopamine itself isn't possible, because dopamine doesn't cross the body's blood-brain barrier. Levodopa, on the other hand, does cross this barrier, but only a small amount actually reaches the brain. Today levodopa is generally combined with carbidopa that targets levodopa to the brain (by limiting its activation in the periphery) increasing the therapeutic index.

During early treatment, side effects from carbidopa-levodopa therapy are usually not a major problem. However, the drug works less evenly and predictably as the disease progresses. As a result, some people may experience involuntary movements (dyskinesia), primarily when the medication is having its peak effects. The length of time for which each dose is effective may begin to shorten (wearing-off effect), leading to more frequent doses.

Another problem that may develop with long-term carbidopa-levodopa usage, the on-off effect, may cause Parkinson's-related movement problems to appear and disappear suddenly and unpredictably. Other side effects may include hallucinations and a drop in blood pressure when standing (orthostatic hypotension). Some people may experience nausea with carbidopa-levodopa therapy.

COMT inhibitors as adjuncts to levodopa: Catechol-O-methyltransferase (COMT) inhibitors are often used alongside levodopa. COMT inhibitors prolong the effect of carbidopa-levodopa therapy by blocking an enzyme that breaks down dopamine. Tolcapone (Tasmar) is a potent COMT inhibitor that easily crosses the blood-brain barrier. But because Tasmar has been linked to liver damage and liver failure, the drug is normally used only in people who aren't responding to other therapies. Entacapone is a COMT inhibitor that shares some of the properties of tolcapone but doesn't cross into the brain. It may help manage fluctuations in the response to carbidopa-levodopa in people with Parkinson's disease. Entacapone doesn't cause liver problems and is now combined with carbidopa and levodopa in a medication called Stalevo.

Dopamine agonists as important components of the Parkinson's disease arsenal: Although carbidopa-levodopa typically allows people with Parkinson's disease to extend the time they are able to lead relatively normal lives and in many cases is effective for a number of years other treatment options are required. Dopamine agonists are used both as adjuncts to carbidopa-levodopa therapy. Bromocriptine and Permax suffered problems with adverse effects in the past however other dopamine agonists such as romocriptine (Parlodel), apomorphine (Apokyn), pramipexole (Mirapex) and ropinirole (Requip) are all still used.

Selegiline as a strategy for delaying carbidopa-levodopa initiation: Selegiline (Eldepryl) is another commonly used therapeutic. This product is an MAO-B inhibitor that limits the breakdown of both naturally occurring dopamine and dopamine formed from levodopa. Selegiline may delay the need for carbidopa-levodopa for about a year, and when taken with carbidopa-levodopa, may enhance the drug's effectiveness.

Parkinson's disease represents a multi-billion dollar market for the pharmaceutical sector: In 2006, the global sales of Parkinson's disease therapeutics were $3.1bn up by 11% from $2.5bn in 2005. Revenues of approved Parkinson's disease drugs across the major markets (US, Japan, France, Germany, Italy, Spain and the UK) totaled over $2.2bn in 2006, with revenues expected to exceed $4.6bn by 2012.

While it may seem distasteful to some talking about a disease as distressing as Parkinson's in terms of dollars, the size of the Parkinson's disease market is driving pharmaceutical activity which will hopefully improve options available to patients. We are currently seeing a climate of change in this market. A number of key drugs are approaching the end of their patent life while other new products are about to enter the market.

The future of Parkinson's disease: The leading therapeutics expected to change the Parkinson's disease market dynamics will include GSK's Requip Once-daily ER, UCB-Schwarz's Neupro and Teva/Lundbeck’s Azilect. Requip ER received an approvable letter from the FDA in Dec. 2007, while at about the same time UCB filed for Neupro. Other key compounds predicted for success include Kyowa Hakko’s Istradefylline, Merck-Serono/Newron’s Safinamide.

The new wave of Gene/cell Therapy compounds that have revealed positive initial clinical data, thus Neurotrophic growth factors (NGF), either to be injected directly into the brain are also tipped for potential market success. Ceregene’s Neuturine, Neurologix’ GAD (glutamic acid decarboxylase) amongst other similar drugs, will add to the present Parkinson's disease therapeutics that will expand revenue growth in the long-term.

More information on Parkinson's disease: LeadDiscovery currently lists over twenty in depth reports on various aspects of Parkinson's Disease (click here) plus over 200 journal articles (click here). To keep track of all activity in the Parkinson's Disease arena subscribe to DailyUpdates-Neurodegenerative Diseases [see todays edition here]


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