MS Blog

Gilenia (FTY720, fingolimod) heads to a FDA Advisory Committee June 10 for review.   Gilenia may become the first oral treatment for MS.  Gilenia is a 0.5 mg capsule taken daily.  Gilenia blocks certain immune cells from leaving lymph nodes, preventing attack on the brain and spinal cord.   In the FREEDOMS trial, Gilenia reduced new relapses by 54%, reduced the likelihood of disability progression by 30% and reduced active contrast MRI lesions 82%.  Risks include slowing heart rate with the first day of treatment, swelling in back of eye (macular edema), mild blood pressure elevation, liver blood test abnormalities and potential serious infection.

Ampyra is FDA-approved to help walking in people with MS.   Improvement was seen in 35-43% of patients in trials.  Four out of 229 patients did have seizures during the extension phase of one trial after the main part of the trial ended.  A big concern is driving restrictions which vary state by state if you have a seizure.

Failed treatments recently studied in MS:   Aricept (Donepezil) for thinking and memory,  Lipitor for first attack of MS, and Omega 3 Fatty Acids (Fish Oil) for depression in MS.

CCSVI Update:   Dr. Zamboni reported at the American Academy of Neurology Meeting in Toronto that 90% of MS patients and none of 45 non-MS patients had vein blockages.  Interestingly,  these percentages were very different from Dr. Zivadinov’s announcement of 56% of MS patients and 22% of healthy control patients had vein blockages.  An independent, multi-center study is necessary to confirm whether vein blockage is indeed more common in MS.  A study of 16 MS patients (all happen to have CCSVI) showed increased iron deposits in parts of the deep brain (thalamus and hippocampus) on MRI.  However, these parts of the brain are not typically involved in MS.  Iron can be found in clean-up cells called microglia and in cells that make myelin called oligo’s.  Therefore, iron from red blood cells into the brain from vein occlusion seems hard to prove based on this observation alone.  Reduced blood flow in the brain and decreased cerebrospinal fluid flow rate were also reported in CCSVI, but no connection was made between the actual veins that were occluded to the side of the brain with decreased blood flow.

An antibody blood test is being developed to tell whether you have been exposed to the virus that can cause the brain viral infection called PML, progressive multifocal leukoencephalopathy.   Biogen Idec and Elan are working on an antibody test to the JC virus. The JC virus is detected in 50-60% of adults.  Eleven MS patients treated with Tysabri who developed PML had previous blood samples stored.  All of these patients did have JC virus antibodies in the blood which means that they had been previously been exposed to the virus before developing the brain viral infection PML. 

Further verification of the test will be required.  If you do not have antibodies to the virus, your PML risk should be extremely low if the preliminary result hold true.  There have been 31 cases of PML reported in over 48,000 currently treated patients.

Biogen Idec Inc. at JPMorgan Healthcare Conference Tuesday, January 12, 2010 http://investor.biogenidec.com

The U.S. Food and Drug Administration approved Ampyra (dalfampridine) extended release tablets to improve walking in patients with multiple sclerosis.  In clinical trials, patients treated with Ampyra ( pronounced am-PEER-ah) had faster walking speeds than those treated with an inactive pill (placebo).

Ampyra is a compound that blocks potassium channels which allows nerves to transmit impulses better.  Two phase III trials of Amprya 10 mg twice a day showed benefits in some people with MS on their ability to walk 25 feet. 

In the first study, 72 patients were treated with placebo and 228 patients were treated with Ampyra over 14 weeks.  Of the 35% of patients who responded to Ampyra, the average change in walking speed increased 25%.

In the second study, 119 patients were treated with placebo and 120 patients were treated with Ampyra over 8 weeks.  43% of treated patients responded.   Ampyra worked in all MS types including relapsing remitting, secondary progressive and primary progressive disease.

The side effects of Amprya include dizziness, trouble sleeping, headache and fatigue.  Although these two trials did not report any seizures, seizures have been reported in people on higher doses of the same active chemical also called 4-aminopyridine.  One seizure can legally prevent you from driving for 6 months in some states.  4-aminopyridine capsules can be made at some compounding pharmacies, but Ampyra will soon be widely available.

Goodman AD. AAN 5/1/07; ECTRIMS 9/20/08 P909.

Paolo Zamboni from Italy discovered that the draining veins from the brain (internal jugular veins) and from the spinal cord (azygous vein) are often blocked or narrowed.  The theory of CCSVI (chronic cerebrospinal venous insufficiency)  is that blood can then back flow into the veins of the brain and spinal cord, leading to iron deposition and blood vessel wall inflammation.

Zamboni performed a trial of opening of the vein blockages with angioplasty in 65 MS patients.  Patients had less relapses and MRI activity after treatment, but there was no comparison group that got a fake “sham” procedure.  Previous trials of patients on no treatment (placebo group) show less relapses and MRI activity over time naturally so follow-up larger studies are needed to see if this treatment is really effective.   There also has been reports of a fatal brain bleed after stenting and a stent moving into the heart so trials will be necessary to see if stenting works if indeed people with MS have more frequent vein blockages.

Overall, an intriguing observation that needs to be verified at other centers.  Is the vein blockages causing MS or simply the result of MS inflammation on the veins?    Further research is needed!

A brain viral infection called PML (progressive multifocal leukencephalopathy) has now been reported in 24 people with MS since being available again in 2006.   Since September 30, 2009,  approximately 46, 200 patients are currently being treated with Tysabri including about 13,400 on treatment for more than 2 years.  Although no known cure exists for PML,  plasmapheresis (a procedure like kidney dialysis)  can be used to help remove the Tysabri antibody from one’s circulation.  Four of the 24 patients have died from the infection.

Watch the Web Event “Advances in  MS Research”.  Back from the ECTRIMS meeting in Dusseldorf, Germany in September,  Dr. Singer discusses in this video new research on repairing myelin, stem cells, progressive disease, and oral pills for MS.

Extavia was FDA-approved for the treatment of relapsing forms of MS.  The therapy is also indicated for patients who have experienced a first attack of MS and have MRI changes consistent with MS. 

Extavia is interferon beta-1b.  Interferon beta-1b was the first FDA-approved treatment in 1993.   The version of interferon beta-1b available for the past 16 years has been Betaseron.  Novartis, who temporarily owned the plant making interferon beta-1b,  has made an arrangement with Bayer, makers of Betaseron, to brand and market their version Extavia.  Now we have two names for the same medicine made in the same plant!

The key will be support for those living with MS:   injection training, nursing support, reimbursement specialists and out-of-pocket costs.   Novartis is committed to MS and working on additional treatments including the daily oral experimental medication FTY720 that will likely go to the FDA for review before the end of 2009.

Watch Dr. Singer’s Web Event “Overcoming MS Fatigue”. http://www.mslivingwell.org/flv/061509-final-2.flv

The American Academy of Neurology annual meeting is in Seattle the week of April 27-May 1, 2009.  

Oral Cladribine reduced relapses by 58% vs. placebo based on the lower of two doses.  The CLARITY trial studied 1326 MS patients over two years.  More patients were relapse free (80%) on treatment with the lower dose than on placebo (61%).  The patients on the low dose of cladribine were 33% less likely to progress in disability.  T1 contrast lesions dropped 86-88% on treatment.  Side effects included low white counts (22-32%), shingles (2%), and some hair loss (3.5%).  One treated patient died with tuberculosis.

FTY720 oral daily treatment compared to Avonex injections reduced relapses 52%  on  the lower dose of FTY720.  The TRANSFORMS  trial studied 1292 patients for 1 year.  More patients were relapse free (83%) on FTY720 than on Avonex (69%).  Side effects and risks included transient slowing of  heart rate and 8 cases of back of the eye swelling (macular edema).  Three cases of melanoma skin cancer were discovered on first dermatology evaluation as part of the trial monitoring.  One death from severe chicken pox in someone also receiving steroids who was never vaccinated or exposed as a child.  One death from herpes encephalitis with a delay of 1 week of diagnosis and treatment.  The MS Center for Innovations in Care was a trial site for this international study.

Rituximab antibody treatment was not helpful in primary progressive MS  overall based on a study of 439 patients.  Rituximab seemed to be effective in the 25% of patients with T1 Contrast lesions on their baseline scan, which is a marker of ongoing active brain inflammation.   

Ginseng, unfortunately, wasn’t very effective for fatigue in a small trial. 

Namenda, an Alzhemier’s medication, did not help thinking in people with MS.

Smoking before age 17 can increase the risk of developing MS 2.7 times.

ATL-TV1102 is a treatment that binds to DNA strands.  The treatment affects a molecule important for white blood cells to cross into the brain. The cumulative number of T1 contrast brain lesions dropped 67% over 12 weeks on treatment.

Watch Dr. Singer’s Web Event “Dealing With Multiple Sclerosis Symptoms”.