What Do Bile Acids Have To Do With Parkinson’s?

Possibly plenty, according to research published in Neurology, September 2015.

There are several genetic forms of Parkinson’s, which are usually seen in patients with very young onset of disease. An autosomal dominant form, meaning that each child of an affected parent has a 50% chance of having the gene termed LRRK2 affects function in the mitochondria. This is the organelle in the cell that generates energy.

Using a cell culture-based technique, researchers tested about 1000 approved drugs and 500 naturally occurring compounds to see if they improved the function of this organelle. They found that there is a drug that is approved for treatment of primary biliary cirrhosis, a disorder of the liver, that has a beneficial effect. It is termed UDCA (ursodeoxycholic acid).

This drug enters the brain, and safety and tolerability studies in patients with Parkinson’s will very likely proceed. It is an entirely new method of treating Parkinson’s.

Can Injections Of Neurotrophic Factors Into The Brain Help Parkinson’s?

Not according to a recent study. This involved surgically treated patients compared with those randomized to sham surgery in order to eliminate placebo effect. Injections of the neurotrophic factor neurturin into areas of the brain affected by Parkinson’s, specifically substantia nigra and putamen, were done, and patients were assessed at 15 months. There was no difference between the 2 groups. The procedure was generally safe though 2 patients had small brain hemorrhages. A previous similar study also showed no benefit.

Parkinson’s patients should be aware that both exercise and coffee consumption have been shown to improve symptoms. These strategies probably lead to increased trophic factors in the brain, and benefit can be achieved without the added risk of a transplant.

See Annals of Neurology, August 2015.

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The Yuck Factor In MS

What do bacteria in the gut have to do with MS? Research in this field is new and exciting. The gut microbiome is the community of bacteria that live in the intestines in humans. There are as many as 500 trillion bacteria and other organisms of different species. The gut may be the largest lymphoid organ in the body and critical for development of autoimmune diseases, such as rheumatoid arthritis and multiple sclerosis.

Recent studies show that mice raised in a germ-free environment have no bacteria in their gut, and when they are treated with an antigen which causes an autoimmune disorder which is not MS but has some features of MS, they cannot mount an immune response and do not develop this disease. Mice raised in a normal environment do. When the mice who have been raised germ-free are fed feces, they then develop the disease.

It has been known for years that children treated with antibiotics early in life have a higher risk of developing autoimmune diseases such as eczema and asthma. There are thus protective organisms in the gut.

Dr Howard Weiner presented research at the 2015 Annual Meeting of the CMSC. His group studied patients with MS on disease-modifying treatments compared with patients not treated. Treated patients had different colonies of bacteria than those who were not being treated, and after given appropriate medications, the bacteria in the untreated patients in fact were altered.

This research holds great promise in understanding MS, as for years, it has been suspected that an infectious agent is the triggering “antigen.” It will hopefully lead to new and more effective therapies.

The Graveyard Of Alzheimer’s Drug Trials

Can we prevent or slow the progression of Alzheimer’s disease? The short answer is no.

Many “observational” trials of drugs or supplements have had positive results, but all these compounds fail when subjected to rigorous clinical trials.

The list seems endless: nonsteroidal anti-inflammatory drugs, antihypertensives (although intuitively, treatment of hypertension should reduce the risk of Alzheimer’s), hormone replacement therapy, intensive control of blood sugar in diabetics. The following nutritional supplements have also been shown to be ineffective: vitamin B12, folic acid, and vitamin B6 with the hope that they lower homocysteine; fish oil or omega-3 fatty acids, which contain DHA; flavonoids; and high-dose vitamin E (2000 units a day).

Monoclonal antibodies against amyloid have generated the most buzz recently. All have failed in Class I trials, which are randomized, double blind, placebo-controlled, probably because patients are treated too late in the course of the disease. New trials are identifying patients who have normal cognition but are at risk for Alzheimer’s, specifically “healthy elderly” who have positive amyloid PET scans. In fact, a subanalysis of a recent large monoclonal antibody trial showed that the mildest group seemed to benefit. Results of these studies will not be available for several years.

Parkinson’s And A Diabetic Drug

Coffee has been consistently shown when drunk in large amounts to reduce the risk of developing Parkinson’s. Also, patients who smoke cigarettes have a lower risk of Parkinson’s. It has been hard to understand why this should be so, but recent studies point to the fact that Parkinson’s disease patients, because they have less dopamine in the brain, tend not to have “addictive personalities” and tend not to smoke cigarettes. If they do, they find it much easier to stop than people without Parkinson’s or those who do not develop Parkinson’s in the future.

Now, 2 widely used antidiabetic drugs in the glitazone category, including Avandia and Actos, seem to reduce the risk of developing Parkinson’s. This large study included over 44,000 people using the glitazone medications compared to 120,000 using other antidiabetic medications.

The point is not to put everyone on these medications to prevent Parkinson’s. Rather, it is to understand why these beneficial effects do occur and use this information to help develop treatments and especially neuroprotection for patients who already have Parkinson’s.

Searching For Therapies For Progressive MS

There are now 11 medications, FDA approved, for relapsing and remitting MS. Other than Novantrone, which is no longer used because of safety issues that were worse than initially predicted, no medication has been approved for progressive MS.

The current thrust of research is neuroprotection rather than anti-inflammatory effects. Below is the summary of studies presented at the 2015 CMSC Annual Meeting.

Lamotrigine (Lamictal) is a sodium channel blocker, widely used to treat epilepsy. The point is to block the sodium channels on the axon and on cells in the brain termed microglia. This technique has proven effective in animal models but so far not consistently in human trials. In one study at 2 years of patients with secondary progressive MS, patients who received the medication had more brain atrophy than controls, though this recovered partly after treatment was stopped. Despite this, there was improvement in the timed 25-foot walk and a reduction in serum neurofilament levels. These levels correlate with brain tissue loss and disability.

Phenytoin (Dilantin), another antiepileptic drug which affects sodium channels, was tested in acute optic neuritis. Patients on the medication had 30% less atrophy in the retinal nerve fiber layer.

Biotin is a coenzyme and widely used for hair thinning and to improve nail growth. Surprisingly, it was found effective in patients with primary and secondary progressive MS, improving the disability scale and the timed 25-foot timed walk. Very high doses were used, and patients would need to take 30 pills daily at the currently available over-the-counter doses. More research is planned.

Amiloride is a medication that treats blood pressure. It also affects an ion channel within axons and within certain brain cells called oligodendrocytes. In one study, it reduced the rates of brain atrophy and damage to the white and grey matter in patients with primary progressive MS.

Riluzole is the only medication approved by the FDA to treat ALS (Lou Gehrig’s disease). In a small study, it seemed to reduce the rate of atrophy in the cervical spinal cord and decrease the development of T1 lesions in the brain in MS patients. These lesions are a marker of atrophy and disability.

Fluoxetine (Prozac) is a widely used antidepressant in the SSRI class. In fact, it was the first in that class approved by the FDA. In some studies, it protects against loss of axons in the brain. A large clinical trial termed MS-SMART is currently recruiting patients to test this further.

Finally, a trial termed SPRINT-MS will test whether the medication called ibudilast can reduce brain atrophy in patients with secondary and primary progressive MS.

To locate clinical trials, go to ClinicalTrials.gov. That site contains every trial registered in the US.

Why Are Older Women Prone To Chronic Pain?

Why Are Older Women Prone To Chronic Pain?
Preventing obesity may reduce the burden of chronic pain.

Obesity is the key. Pain intensity and interference of pain with daily life among older adults are more common in women and are associated with obesity. Inflammatory compounds are released from visceral fat tissue, and obesity is considered to be a proinflammatory state. Chronic inflammation is in turn associated with pain.

A new study found that an inflammatory marker termed C-reactive protein (CRP) was higher in older obese women who had chronic pain. This association was not seen in men, and this finding is unexplained.

The message is that treating and especially preventing obesity may reduce the burden of chronic pain.

This study was presented at the American Academy of Neurology 2015 Annual Meeting. The lead study author was Vahid Eslami, MD.