Neurologist Dan Milder's SP & PP treatment Hypothesis

[CureOrBust]

I accidental flicked onto a "press club" interview on TV of this doctor who thinks he MAY have found a possible treatment for SP & PP MS. He was very reasonable (he was coming across as arrogant, but it could of been misdirected anger) and all he was saying is that he thinks it should be investigated, he is not saying its an absolute truth. He seemed a little upset that considering there is no real treatment for these patients, an investigation into the results he has seen was called for. He didn't appear interested in running the trials himself, but was almost begging that a trial be run.

The following page is a copy of a Time magazine article ==> http://www.geocities.com/Athens/7720/time.htm

Neurologist Dan Milder was running out of ideas on how to treat one of his multiple sclerosis patients. Diagnosed less than two years ago, "Samantha" was going down fast. Her vision was blurred and she was unable to see color; she was incontinent and incoherent, and her balance was so poor she was confined to a wheelchair

Milder adjusted her drug regimen, combining a new MS drug with an older one. Her response stunned him. Within weeks, she was mentally sharper and her vision had improved. Within months, she was able to jog. Incredulous, Milder put another patient onto a similar program. Again the results were impressive. He tried it on a third, also with success.

Exactly why these drugs seem to work, Milder isn't sure. But he theorizes that the onset of progressive MS, rather than being an endpoint for worthwhile treatment, may in fact be a window for a more effective drug assault that gives myelin a chance to regenerate.

There is more, the whole article is worth a read. I think the drugs involved are the combination of Azathioprine and interferon beta-lb.

[dignan]

That sounds interesting. I had a look in Pubmed and it turns out, some trials have been done, and it all looks pretty good.



Serum immunologic markers in multiple sclerosis patients on continuous combined therapy with beta-interferon 1a, prednisone and azathioprine.

Mult Scler. 2006 Oct;12(5):652-8.
Braun Hashemi CA, Zang YC, Arbona JA, Bauerle JA, Frazer ML, Lee H, Flury L, Moore ES, Kolar MC, Washington RY, Kolar OJ.
Indiana Center for Multiple Sclerosis and Neuroimmunopathologic Disorders, Indianapolis, IN 46260, USA.

Break-through symptoms (BTS) in multiple sclerosis (MS) patients on beta-interferon (beta-IFN) monotherapy are most frequently treated with a brief administration of steroids. Here, we report the results of monitoring serum immunologic markers recorded at three-month intervals for 1.5 years in responders to beta-INF 1a (Avonex) monotherapy (n =21) and MS patients placed on Avonex with prednisone (n =83) and Avonex, prednisone and azathioprine (AZA) (n =21) because of BTS.

Compared to 23 healthy controls, patients on Avonex monotherapy and Avonex with prednisone, in individuals on Avonex, prednisone and AZA, a significant decrease in serum concentration of soluble intercellular adhesion molecule-1 (sICAM-1) (P=0.001) was established. Combined therapy with Avonex, prednisone and AZA was associated with a significant increase in the serum level of interleukin (IL)10 (P <0.001). Compared to Avonex monotherapy, combined therapy suppressed the serum level of IL12p40, antagonized elevation in the serum concentration of soluble IL2 receptor (sIL2R) and inhibited an increase in the serum soluble CD95 (sCD95) molecule. In patients studied, no significant differences in the serum level of IL18 and tumor necrosis factor-alpha (TNF-alpha) were established.

These findings are important in understanding some of the immunoregulatory mechanisms induced by combined therapy in MS.



Optimization of the safety and efficacy of interferon beta 1b and azathioprine combination therapy in multiple sclerosis.

Mult Scler. 2005 Apr;11(2):169-74.
Pulicken M, Bash CN, Costello K, Said A, Cuffari C, Wilterdink JL, Rogg JM, Mills P, Calabresi PA.
Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.

We conducted an open-label pilot clinical trial to evaluate the safety and efficacy of adding oral azathioprine to the treatment regimen of 15 multiple sclerosis patients breaking through monotherapy with interferon beta-1b. There were no serious adverse events. Gastrointestinal side effects and leukopenia were the most common adverse events and limited dose escalation. There was a 65% reduction in the number of gadolinium-enhanced magnetic resonance imaging (MRI) lesions on combination therapy compared to the baseline values (P =0.003). A total WBC count less than 4800/mm3 was the best predictor of MRI response.



Azathioprine and interferon beta(1a) in relapsing-remitting multiple sclerosis patients: increasing efficacy of combined treatment.

Eur Neurol. 2004;51(1):15-20. Epub 2003 Nov 18.
Lus G, Romano F, Scuotto A, Accardo C, Cotrufo R.
Department of Neurological Sciences, Faculty of Medicine of the Second University of Naples and the Centro Interuniversitario di Ricerca in Neuroscienze, Naples, Italy. giacomo.lus@unina2.it

Current treatments of relapsing-remitting multiple sclerosis (RRMS) with immunosuppressive or immunomodulatory drugs have been shown to modify the course of the disease in a significative number of patients. However, in many cases, the response to either interferon beta (IFN-beta) or azathioprine (AZA) treatments was not satisfactory and new therapeutic approaches are needed.

We studied clinical and MRI efficacy, safety and tolerance of AZA and IFN-beta(1a) combined therapy in 23 patients with clinically definite RRMS, who had not previously been responsive to either monotherapies. Our cases were divided into three subgroups: 8 previously untreated patients (subgroup A) with at least 2 years of natural course of the disease, 8 patients (subgroup B) previously treated with AZA for 2 years and 7 patients (subgroup C) previously treated with IFN-beta(1a) for 2 years. The baseline Expanded Disability Status Scale (EDSS) ranged from 2 to 4 in all subgroups. All patients completed 2 years of combined treatment with a dose of AZA adjusted to reduce lymphocyte count down to 1,000 +/- 100/microl in association with IFN-beta(1a) at a dose of 6 MIU every other day.

The mean number of relapses during the combined treatment period was significantly lower than that observed before combined therapy in all the three subgroups. Also, the mean Delta EDSS score was significantly lower during combined treatment than in monotherapy in subgroups B and C. Moreover, after 2 years of combined treatment, the number of new T(1) hypointense lesions, the number and volume of proton density/T(2) hyperintense lesions and the gadolinium enhancement of T(1) hypointense lesions were significantly lower than before combined treatment. After 2 years of treatment, this combination therapy appears to be safe and well tolerated and no serious side effects were reported.

Despite some limitations of our study design, the information regarding efficacy, safety and tolerance of the association of AZA and IFN-beta is most encouraging.

[CureOrBust]

the above trials (one explicitly) is for relapsing-remitting. This guy was talking secondary and primary only. I have to admit that I got a little excited that someone was having such success with SP & PP (he was trying to distance himself from RR from memory) that I didn't bother to check myself, thanks.

[dignan]

The middle study above from Johns Hopkins included SP and RR patients. It was a small study though.

[MaggieMae]

Azathirprine is also known as Imuran. In the 1970's my husband's doctor was using this drug for his patients. He wanted my husband to go on the drug, but he cautioned that it could be lethal. I still have the papers he gave us to read on the drug. He said the drug was not approved for MS; it was only approved for cancer. My husband decided not to take the Imuran because he always recovered when he had an attack (took ACTH then). I always regret that decision. An old friend of my husband's also was treated by the same doctor. She took the Imuran shortly after she was diagnosed. That was nearly 40 years ago. She is still walking around with no assistance and doing all the things she loves. I talked to her last year. If I remember correctly, she said that she never had an attack after she started the Imuran. She said she remembered getting so hot (sometimes) that she would go outside even in the snow to cool down. She hasn't been on the Imuran for awhile now. Doesn't take anything for MS. I can't remember how long she took the Imuran, but I think it was for at about 20 years. Thirty years ago this doctor said "MS is always doing damage even when you are not having an attack".

I have read many articles on Imuran. Google Dr. Jeff Greenstein from the MS Institute in Philadelphia, PA. He uses the drug also.

This is why when I read about Tim with Tovaxin or Chris with the Revimmune, I think, GO FOR IT. Stop that damage as soon as you can. Now, my husband, who always recovered has slowly declined in the last 10 years and can no longer walk without assistance.

[Brainteaser]

Cure,

Dr Milder's combination therapy of Imuran and a CRAB has been around for a while. I note the document you quote from is dated 2002. So, have you seen anything more recent?

Around that time there was a lot of local publicity about the treatment. I contacted him in Sydney and he referred me to a colleague in Melbourne, who put me on the treatment for a year or so, without success.

I'm not sure what Dr Milder is up to at present but he was quite approachable at the time and being in Sydney, it should be convenient for you.

Regarding combination treatments, I think there could be something to it. Further to dignan's post, Ian (bromley) posted of some studies in the UK about a year ago. Also, on the recent Dr Vollmer video, he mentioned the potential of combinaion therapies............although HarryZ (bless him) would probably say that it is a conspiracy by the drug companies to extract twice as much money from patients!