ß-2 MicroGlobulin (ß 2M) is a low molecular weight protein located ExtraCellularly and associated with Class 1 Antigens of the Major Histocompatibility Complex and is considered a marker for disease activity in Immune Disorders.

Cladribine (2-Chloro-2-DeoxyAdenosine, 2-CDA) is a potent LymphocyTotoxic agent under investigation in the treatment in MS patients.

As ß 2M levels may indicate inflammatory events in CNS we determined CSF-ß 2M and Serum ß 2M levels in patients with Relapsing/Remitting MS before and after Cladribine treatment as well as in a control group.

There was a significant ß 2M decrease in Sera but not in CSF in MS patients after the Cladribine treatment.

Associated with a slight but significant clinical improvement measured by Kurtzke's Expanded Disability Status Scale.

We also found a significant decrease in sICAM-1 level in CSF but not in Sera in MS patients. The data support a role of Cladribine in MS therapy and deliver new information on Cladribine Immunological effects in MS patients.

In a recent communication, Goodin [1] analyzes several clinical trials to point out serious flaws in both design and interpretation that may invalidate the conclusions that are drawn.

We agree with Goodin [1] that the design of clinical studies, particularly of a disease as complex as Multiple Sclerosis, is extremely difficult.

Indeed, a perfectly designed and executed clinical study is a goal that is never achieved because of the problems inherent in providing care to patients while attempting to evaluate a therapeutic modality.

Specifically, in the study of Multiple Sclerosis, none of the clinical trials of the use of Interferons could be considered fully satisfactory:

Blinding is actually impossible because of the symptoms that are experienced by patients when they receive active drug but not when they receive placebo.

It is quite fashionable and not at all difficult to find problems in the conduct of clinical studies; indeed, if all clinical studies with flaws were discarded, there would be no acceptable clinical studies.

Objective
To evaluate the safety and efficacy of two doses of Cladribine in patients with Progressive MS.

Background
Treatment of Progressive MS patients with Cladribine in a previous single-center, placebo-controlled clinical trial was associated with disease stabilization.

Methods
In the current study, 159 patients with a median baseline Kurtzke's Expanded Disability Status Scale (EDSS) score of 6.0 were randomly assigned to receive placebo or Cladribine.

0.07 mg/kg/day for 5 consecutive days every 4 weeks for either two or six cycles (total dose, 0.7 mg/kg or 2.1 mg/kg, respectively), followed by placebo, for a total of eight cycles.

Thirty percent had Primary/Progressive MS (PPMS) and 70% had Secondary/Progressive MS (SPMS).

EDSS and Scripps Neurologic Rating Scale (SNRS) scores were assessed bimonthly and MRI was performed every 6 months. The primary outcome measures was disability (mean change in EDSS).

Results
Mean changes in disability did not differ among the groups at the end of the 12-month double-blind phase.

Both Cladribine treatments were superior to placebo for the proportion of patients having Gadolinium-enhanced T₁
lesions and for the mean volume and number of such lesions (p ltoreq 0.003).

Differences were statistically significant at the 6-month evaluation time, with gtoreq90% reduction in volume and number of enhanced T₁
lesions, which was maintained through final evaluation.

This effect segregated largely with the SPMS group. The T2 burden of disease showed a modest improvement in Cladribine-treated patients and worsened in placebo-treated patients. Most adverse events were mild or moderate in severity and not treatment limiting.

Conclusion
No significant treatment effects were found for Cladribine in terms of changes in EDSS or SNRS scores.

Both doses of Cladribine produced and sustained significant reductions in the presence, number, and volume of Gadolinium-enhanced T₁
Brain lesions on MRI.

And, Cladribine 2.1 mg/kg reduced the accumulation of T2 lesion load. Cladribine at doses up to 2.1 mg/kg was generally safe and well tolerated.

We conducted an 18-month, placebo-controlled, double-blind study to evaluate Cladribine in the treatment of 52 patients with Relapsing/RRemitting Multiple Sclerosis.

Patients received either placebo or Cladribine 0.07 mg/kg/day by subcutaneous injection for 5 consecutive days as six monthly courses for a total cumulative dose of 2.1 mg/kg.

Analysis of results revealed a statistically significant favorable effect of Cladribine on the joint frequency and severity of relapses and Magnetic Resonance Imaging (MRI) findings.

MRI-enhancing lesions were completely suppressed in the Cladribine patients by the sixth month of treatment.

Mild segmental Herpes Zoster occurred in two Cladribine treated patients and one patient receiving placebo.

Otherwise, there were no side effects or adverse events. We conclude that Cladribine shows promise as a treatment for Relapsing/Remitting Multiple Sclerosis.