The MSA conference in San Diego on October 1st and 2nd 2010 was very enjoyable and informative. Vera James and Judy Biedenharn did an excellent job organizing and hosting the event.
On Friday evening there was an opportunity to meet many of the attendees informally at social night. On Saturday morning there were three doctors who presented. Then after lunch there was a Q&A session followed by a break out session where patients and caregivers split into separate groups for general discussion/sharing.
Dr. Tom Chelimsky honored Don and Sylvia Summers for their years of dedicated service to MSA patients and families by presenting plaques with a wonderful inscription. We also all signed a card to send Don thanks. Don has stepped down as president of the SDS/MSA Support Group for health reasons. Many would have talked to Don on the toll free support line or met him at past MSA conferences which he was dedicated to organizing.
There was also a special guest appearance by “Tim’s Shoe” who posed for many photos which will soon be shared on the “Where is Tim’s Shoe” facebook page, another avenue for MSA awareness.
Dr. Stephanie Lessig from UC San Diego is carrying on with the MSA research work started by Dr. Cliff Shults. She is a member of the MSA Consortium at UCSD and Mayo Clinic, along with Dr. Sid Gilman and Dr. Phillip Low.
Dr. Lessig spoke on “Hot Topics in MSA: Biomarkers and Neuroprotection”.
An example of a biomarker for heart disease is high cholesterol. Dr. Lessig pointed out that we do not yet have a similar biomarker that indicates MSA and that changes over time. Because of this is it difficult to design clinical trials as there is nothing to measure against. With heart disease we are able to give drugs that lower the cholestrol and we can clearly measure that this is happening. The diagnosis of MSA is all based on the clinical judgement of the neurologist.
Dr. Lessig also spoke on various neuroimaging techniques that are improving the diagnosis of MSA somewhat.
MRI – measures water molecule movement. In MSA, water moves more because structures in the brain have shrunk.
/DWI – Diffusion Weighted Imaging – a form of MRI
SPECT – Single Positron Emission Computerized Tomography – this is a CAT scan after radioactive dopamine is injected.
DTI – Diffusion Tensor Imaging – shows pathways in the brain from the brainstem to the cortex.
PET- Positron Emition Tomography – shows brain activity/energy usage/glucose metabolism rather than brain structure.
Neuroprotection is a therapeutic strategy that is aimed at preventing the ultimate result of a neurodegenerative disease process – something that slows or alters the disease.
In MSA, current medications available only treat symptoms such as orthostatic hypotention/low blood pressure.
Neuroprotection would prevent some aspect of the disease, perhaps from the start or would interrupt the disease progress in some way. For example, the way aspirin will prevent stroke.
There are currently several treatment agents under study. Search for MSA under: www.clinicaltrials.gov
For Blood Pressure symptoms (to increase standing blood pressure):
3. Fluoxetine (Prozac)
4. Mesenchymal Stem Cell
Droxidopa and Fluoxetine increase standing blood pressure by increasing the “fight or fight” neurochemical called norepinephrine.
Fipamezole increases standing blood pressure by working to constrict blood vessels.
Nebivolol decreases lying blood pressure by working to relax blood vessels.
Lithium and Minocycline, both shown to reduce cell deaht in cell culture, both investigated in several neurodegenerative disorders (Parkinson’s and Alzheimers)
IVIG ( IV Immunglobulin) is an anti-inflammatory used in autoimmune conditions
Rasagiline(Azilect) – a transgenic mouse model of MSA showed that rasagiline reduced nigral stratal and cerebellar cell loss in the mouse and can be considered a promising disease-modifying candidate for testing in humans with MSA. A clinical trial is underway to test this. Volunteers are needed. There are 51 clinical study sites in 12 countries. 140 patients are needed. Participation in an imaging substudy will be offered to enrolled subjects at selected sites.
To be included in the Rasagiline for MSA study you must be:
– greater than 30 years s old with a diagnosis of possible or probable MSA of the Parkinsonian subtype (MSA-P)
– less than 3 years from documented MSA diagnosis
– anticipated survival of greater than 3 years in the opinion of the investigator
– willing and able to give informed consent
There will be investigator evaluations at the screening visit and study – weeks 0, 12, 24, 36 and 48
Phone visit and assessment between study visits at weeks 6, 18, 30 and 42.
See list of study sites at:
Autologous Mesenchymal Stem cell trials are underway in Korea. This makes use of the patients own skin cells . Injected back into artery and vein. There are questions as to how these get to the brain and in the proper place within the brain. More tangible results are needed.
Dr. Eliezer Masliah of the Departmet of Neurosciences and Pathology, University of California San Diego presented on the topic of “Multiple System Atrophy: Pathogenesis and Experimental Treatments”
Dr. Masliah started out by saying how much he appreciated the opportunity to meet with MSA patients at the conference. He works all day in a laboratory dealing with cell cultures so it is very heartening for him to be able to connect with patients who give him more motivatation in his work.
What he and his team are doing is very exciting and encouraging. I know many people think there is nothing being done in MSA research but this is just not so. Dr. Masliah and many others in pathology laboratories are working hard to unravel this very complicated mystery called MSA.
Because of very generous brain donations from MSA patients, Dr. Masliah is able to study exactly what is happening in the brain and is trying to make sense of it.
What is known so far is that in the brain there are neurons and there are neuron helper cells called glial cells. In MSA it is the glial cells that are affected most. Especially the type of glial cells called the oligodendrocytes. Inside these cells are “glial cytoplasmic inclusions” made up of a protein called “alpha synuclein”. These inclusions are what causes the glial cells to degenerate. Once glial cells degenerate, neurons also die.
Alpha-synuclein is also involved in other neurodegenerative diseases such as Parkinson’s and Alzheimer’s. Supporting research efforts in this area could be key in finding treatments for many neurodegenerative diseases.
Dr. Masliah went over the various ways that the aggregation or clumping of alpha-synuclein could be prevented in mouse models of MSA:
1. anti-aggregation componds could block alpha-synuclein accumulation(rifampicin, flavinoids, poly-phenols)
2. anti-oxidant compounds could block alpha-synuclein conversion(CoQ1, catalases)
3. there could be vaccination/antibodies against alpha-synuclein(passive and active immunization)
He also outlined therapeutic strategies to prevent cell death in mouse models of MSA:
1. Gene therapy with growth factors (GDNF, BDNF, CTNF, IGF-1)
2. Infusion with osmotic minipump of growth factors into the brain (GDNF, BDNF)
3. Therapies with compound that will stimulat endogenous growth factor production (rasagiline and fluoxetine(prozac))
Testing has been done with Rifampicin in mice that have MSA and results show that it reduces alpha-synuclein accumulation. This is very promising research.
Note: There is a clinical trial starting soon for Rifampicin!
Go here to register in the patient database to be notified of when the trial will start
6102 – An Oligo-centered, Randomized, Double-blind, Placebo-controlled Clinical Trial to Assess the Efficacy, Safety, and Tolerability of Rifampicin in Patients with Multiple System Atrophy
Testing has also been done of vaccinations to reduce alpha synuclein accumulation in mice with MSA. Mice were shown to develop antibodies against alpha-synuclein which promotes the clearance of alpha-synuclein from the cells. Clinical trials using this approach are underway in Alzheimer’s patients. Results are expected in 2011.
Dr. Masliah believes that a treatment for MSA might be a combination of several of the above methods. He stressed that in the mice being studied the results were much better if the mice were treated when they were very young, before many symptoms had started. There seemed to be a point at which if a mouse had progressed significantly that the treatment would no longer work. It is therefore very important to be able to find a biomarker for MSA, to diagnose it earlier and begin treatments earlier. This is all very hopeful research and I was so happy to hear from Dr. Masliah at the conference.
Dr. Tom Chelimsky, Board member of the SDS/MSA Support Group, works in the Department of Neurology at Case Western Reserve University & University Hospitals of Cleveland, OH.
His presentation topic was a general one on “MSA” in which he described the history and current thinking on the disease, defined the brain regions involved in autonomic problems, loss of coordination and stiffness of movement. He also offered some practical tips and suggestions in a very informative and entertaining way. I really enjoyed his talk.
What is MSA?
A disorder that causes specific regions of the brain to lose brain cells causing:
– Urinary Incontinence
– Sleep Disorders
– Orthostatic Hypotension
1900 – Sporadic olivopontocerebellar atrophy(sOPCA) was first described by Dejerine and Thomas
1960 – Shy-Drager syndrome described by Shy and Drager
1961 – Striatonigral Degeneration identified by Adams et al
1969 – Graham and Oppenheimer united these three clinical disorders into a single entity and coined the term MULTIPLE SYSTEM ATROPHY
Sub Classification of MSA:
1. MSA-P – Parkinsonian – 58% as initial symptom
2. MSA-C – Cerebellar – 29% as initial symptom
Note: there is no longer a classification of MSA-A – Autonomic, this classification was dropped because both MSA-P and MSA-C include the symptoms of autonmomic or urinary dysfunction.
Statistic: 4.4 people per 100,000 are affected with MSA.
Brain parts affected by MSA:
Pons – part of the brain that controls bladder. The pons shows the hot cross bun sign on an MRI image in MSA
Striatum – these cells are missing in MSA
Basal Ganglia – body and brain pacemaker, temperature control, posture maintenance, harmonize with internal environment.
Cerebellum – matches what the brain is expecting and what the body is expecting. matches movement and sensation. Posture maintenance. Harmonize with external environment.
Tips and Suggestions:
– Exercising: remember water jogging is beneficial but check with your doctor first
– Physical Therapy can help you determine safest way to walk
– Falls my be due to combination of low blodd pressure and brain malfunction
– Salt is often good to add to your diet under physician supervision
– Weat Jobst thigh high stockings and/or abdominal binder, this will force blood to your heart and keep blood pressure up
– See sheet of tips for low blood pressure – (Note there was a handout – Vera may be able to provide a soft copy)
– about 40% of patients with MSA are moderately to severely depressed
– Quality of life is mostly dependent on how much autonomic symptoms are present and depression
– Depression is a treatable added disorder
– 3 types of problems
1. Incontinence – loss of control
2. Inability to void
– Loss of control is due to degeneration of autonomic systems that control the bladder
– Urgency is due to changes in the spinal circuits and in the bladder nerves themselves
– Evaluate for large prostate in men – “Do not have prostate surgery unless the urologist and neurologist have had a conversation”
– Urgency can be treated by medication such as ditropan, detrol, vesicare etc
– Retention – can try meds like hytrin, alpha-blockers but usually difficult to tolerate due to orthostatic hypotension. Alpha-blockers open sphincter and this is counter to keeping blood pressure up.
– Can be combined with medication
– Can be done just before bed and first thing in the morning
– Tailor it to your needs and to requirements of safety
If done more often – less risk to kidneys
If done less often – less risk of Urinary Tract Infections