David R. Strayer, M.D. is the Chief Scientific & Medical Officer of Hemispherx Biopharma, the makers of Ampligen. Formerly a Professor of Medicine at the Medical College of Pennsylvania and Hahnemann University from 1987 to 1998. Board Certified in Medical Oncology and Internal Medicine with research interests in the fields of cancer and immune system disorders. Principal investigator in studies funded by the Leukemia Society of America, the American Cancer Society, and the National Institutes of Health.
- 2015, Low NK Cell Activity in Chronic Fatigue Syndrome (CFS) and Relationship to Symptom Severity
Abstract - "Background: Natural killer (NK) cells act as an immune surveillance against invading pathogens and tumors. NK cell cytotoxicity (NKCC) has been reported to be decreased in patients with CFS. Methods: The objective of this review was to conduct an analysis of available publications that reported NKCC data in CFS in order to evaluate any relationships to case definitions used to define CFS and symptom severity. Results: Of 17 studies that evaluated NKCC in patients with CFS, defined using the CDC 1988 and/or 1994 case definition (CD), 88% (15/17) concluded that NKCC was decreased in CFS patients compared to normal controls. The NKCC decrease was seen using two established methods, 51Cr release (11/13) and flow cytometry (4/4). The mean percent decrease in NKCC using the CDC 1988 CD (66.3%) was significantly greater than that using the CDC 1994 CD (49.7%) (p<0.01). This result is consistent with that of six publications showing a greater decrease in NKCC associated with increased CFS symptom severity based on the lower symptom requirement for the CDC 1994 vs. 1988 CD. In contrast, there was no significant difference in the mean percent decrease in NKCC seen comparing the CDC 1994 CD defined population using the 51Cr release (48.3%) vs. flow cytometry (50.7%) assays (p>0.5). Finally, seven studies investigating the ability of various agents to augment NKCC in patients with CFS showed increases of NKCC with both in vitro exposure (4/5) and in vivo exposure using randomized trials (2/2). Conclusions: Low NKCC is commonly seen in CFS and is associated with increase symptom severity.
- 2015, Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME): Characteristics of Responders to Rintatolimod.
Abstract: "Methods and Findings: In order to better identify responders to rintatolimod, primary and secondary endpoints have been reexamined post hoc as a function of a pre-specified study baseline ET duration >9 minutes. Analysis of improvement in exercise performance at the ≥ 25% and ≥ 50% levels using [exercise tolerance] ET at 40 weeks compared to baseline was performed for the intent-to-treat (ITT) population (n=208) using the pre-specified baseline exercise stratum (baseline ET duration >9 minutes)...This corresponds to increases of ≥ 186 and ≥ 373 seconds for patients receiving rintatolimod, respectively, at ≥ 25% and ≥ 50% improvement responses. A frequency distribution analysis of ≥ 25% improvement, <25% change, and ≥ 25% deterioration in ET from baseline at 40 weeks for the baseline >9 minutes cohort showed net improvement to be 18.3% for the rintatolimod cohort vs. 4.6% deterioration for placebo (p=0.015)...The KPS and Vitality (SF-36 subscale) quality of life secondary endpoints demonstrated similar clinically significant improvements for the rintatolimod cohort as a function of the same ET dichotomization...Conclusions: Using a modified Bruce ET protocol with reduced physical exertion allowed clear identification of patient responders to rintatolimod with severe CFS/ME syndrome. Rintatolimod produced significant enhancement in ET and quality of life indicators in patients able to complete >9 minutes in a modified Bruce ET test. Rintatolimod also reduced deterioration in ET compared to placebo in patients with the poorest initial ET. Exercise endurance >9 minutes in a Bruce protocol modified for patients with CFS/ME provides a method to identify patients most likely to respond to rintatolimod."
- 2012, A double-blind, placebo-controlled, randomized, clinical trial of the TLR-3 agonist rintatolimod in severe cases of chronic fatigue syndrome.
Abstract: "A Phase III prospective, double-blind, randomized, placebo-controlled trial comparing twice weekly IV rintatolimod versus placebo was conducted in 234 subjects with long-standing, debilitating CFS/ME at 12 sites. The primary endpoint was the intra-patient change from baseline at Week 40 in exercise tolerance (ET). Secondary endpoints included concomitant drug usage, the Karnofsky Performance Score (KPS), Activities of Daily Living (ADL), and Vitality Score (SF 36). Subjects receiving rintatolimod for 40 weeks improved intra-patient placebo-adjusted ET 21.3% (p = 0.047) from baseline in an intention-to-treat analysis. Correction for subjects with reduced dosing compliance increased placebo-adjusted ET improvement to 28% (p = 0.022). The improvement observed represents approximately twice the minimum considered medically significant by regulatory agencies. The rintatolimod cohort vs. placebo also reduced dependence on drugs commonly used by patients in an attempt to alleviate the symptoms of CFS/ME (p = 0.048). Placebo subjects crossed-over to receive rintatolimod demonstrated an intra-patient improvement in ET performance at 24 weeks of 39% (p = 0.04). Rintatolimod at 400 mg twice weekly was generally well-tolerated.
- 2005, Exercise capacity and immune function in male and female patients with Chronic Fatigue Syndrome
"Abstract: Hyperactivition of an unwanted cellular cascade by the immune-related protein RNase L has been linked to reduced exercise capacity in persons with chronic fatigue syndrome (CFS). This investigation compares exercise capacities of CFS patients with deregulation of the RNase L pathway and CFS patients with normal regulation, while controlling for potentially confounding gender effects. Thirty-five male and seventy-one female CFS patients performed graded exercise tests to voluntary exhaustion. Measures of peak VO2, peak heart rate, body mass index, perceived exertion, and respiratory quotient were entered into a two-way factorial analysis with gender and immune status as independent variables. A significant multivariate main effect was found for immune status (p<0.01), with no gender effect or interaction. Follow-up analyses identified VO2 peak as contributing most to the difference. These results implicate abnormal immune activity in the pathology of exercise intolerance in CFS and are consistent with a channelopathy involving oxidative stress and nitric oxide-related toxicity."
- 2001, Assessment of Functional Impairment by Cardiopulmonary Exercise Testing in Patients with Chronic Fatigue Syndrome
"Summary - Functional impairment in a population of patients with chronic fatigue syndrome (CFS) was determined by exercise testing. The criteria established by Weber and Janicki (1) were employed because impairment levels are based on maximal oxygen consumption. Oxygen consumption was obtained by cardiopulmonary exercise testing and was used to classify subjects according to the severity of impairment. All the subjects in this study met the CDC case definition (2) for CFS. All patients underwent at least two maximal graded exercise tests in which expired air was collected for assessment of V02max. Data are included for eighty-seven CFS patients, the highest V02 was used for determining impairment. Although all patients met the CDC case definition for CFS, only 35 (40%) would be classified as having greater than “Mild” functional impairment. The highest V02 of any of the patients in this study was 29.5 ml/kg/min, very close to what normative data predicts to be the average maximal value for the entire group. Without a sedentary control group it is unclear if the low V02 in this population is due to the pathology of CFS or results from the inactivity that accompanies the disease. However, use of maximal V02 during exercise can clearly discriminate between levels of functional impairment and may be efficacious for diagnosis of CFS. Additionally, in cases where cardiopulmonary analysis is unavailable, exercise duration on a standardized test may also be employed."
- 1995, Long Term Improvements in Patients with Chronic Fatigue Syndrome Treated with Ampligen
Abstract: "Fifteen patients who fit the CDC definition of chronic fatigue syndrome (CFS) and had evidence of severe reduction in performance levels by low Karnofsky performance scores (KPS) of 20-60 were treated with Ampligen. At baseline most patients showed evidence of cerebral dysfunction by neuropsychological testing, were antigen positive by cell culture assay for human herpesvirus-6 (HHV-6), and displayed reduced performance during exercise tolerance testing, as measured by oxygen consumption. These patients represented a subset of CFS patients with especially severe and sustained symptomatology. Following 1248 weeks of Ampligen therapy, sustained improvements were noted in KPS (p < 0.01). Cognitive function improved including IQ and memory. Oxygen uptake and treadmill duration during exercise tolerance testing was also improved after 24 weeks of treatment (p < 0.01). Reduction in HHV-6 expression as measured by the giant cell assay was significant (p < 0.001). Patients continued to show significant improvement late in therapy, taking 8 to 12 weeks as baseline. It was concluded that while receiving Ampligen, the severely afflicted patients studied here derived long-lasting clinical benefit from the Ampligen therapy."
- 1994, Ampligen inhibits human herpesvirus-6 in vitro.
Abstract: "The recently discovered human herpesvirus-6 (HHV-6) is being associated with an increasing number of conditions in which there is evidence of immunologic dysfunction. A number of widely available antiviral agents have shown little or no activity against the virus. We found that Ampligen [Poly (1): Poly (C12U), a synthetic, mismatched, double-stranded RNA, has potent, previously unexpected antiviral effects. Cells known to allow replication of HHV-6 were infected with the virus and treated with Ampligen under various conditions. When cells were pretreated with Ampligen (concentrations of 100 or 200 micrograms/ml) prior to infection or treated shortly after infection, viral replication was inhibited by 46-98%. At 100 and 200 micrograms/ml, Ampligen also inhibited the DNA polymerase activity of HHV-6 by 42-98%. When lower concentrations of Ampligen (10 and 50 micrograms/ml) were used, only pretreatment of cells, with Ampligen, followed by virus infection and carrying the infected cells with Ampligen, significantly inhibited HHV-6 infection (83.7 and 89.1% respectively). Indirect evidence suggests that Ampligen may inhibit viral attachment to cellular receptors and/or inhibit intracellular maturation of the virus. The above concentrations of Ampligen were not toxic to the cells used in the study. Given these in vitro findings, and the low frequency of toxicity reported with the use of Ampligen, clinical trials of this drug in patients with evidence of reactivated HHV-6 infection would seem to be warranted."
- 1994, A controlled clinical trial with a specifically configured RNA drug, poly(I).poly(C12U), in chronic fatigue syndrome.
Abstract:" In a randomized, multicenter, placebo-controlled, double-blind study of 92 patients meeting the CFS case definition of the Centers for Disease Control and Prevention, the response of several laboratory and clinical variables to an antiviral and immunomodulatory drug, poly(I).poly(C12U), was determined. Measures of clinical response included Karnofsky performance score, a cognition scale derived from a self-administered instrument assessing symptomatology (SCL-90-R), an activities of daily living scale, and exercise treadmill performance. After 24 weeks, patients receiving poly(I).poly(C12U) had higher scores for both global performance and perceived cognition than did patients receiving placebo. In particular, patients given poly(I).poly(C12U) had increased Karnofsky performance scores (P < .03), exhibited a greater ability to do work during exercise treadmill testing (P = .01), displayed an enhanced capacity to perform the activities of daily living (P < .04), had a reduced cognitive deficit (P = .05), and required less use of other medications (P < .05)."
- Hemispherx Biopharma Management
- Strayer, David; Scott, Victoria; Carter, William (2015-07-29), "Low NK Cell Activity in Chronic Fatigue Syndrome (CFS) and Relationship to Symptom Severity", Journal of Clinical & Cellular Immunology: 1–9, ISSN 2155-9899, doi:10.4172/2155-9899.1000348
- Strayer, David R; Stouch, Bruce C; Stevens, Staci R.; Bateman, Lucinda; Lapp, Charles W; Peterson, Daniel L; Carter, William A; Mitchell, William M (8 August 2015), "Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME): Characteristics of Responders to Rintatolimod" (PDF), Journal of Drug Research and Development, 1 (1), doi:10.16966/2470-1009.103
- Strayer, DR; Carter, WA; Stouch, BC; Stevens, SR; Bateman, L; Cimoch, PJ; Lapp, CW; Peterson, DL; Chronic Fatigue Syndrome AMP-516 Study Group; Mitchell, WM (2012), "A double-blind, placebo-controlled, randomized, clinical trial of the TLR-3 agonist rintatolimod in severe cases of chronic fatigue syndrome.", PLoS One, 7 (3): e31334, PMID 22431963, doi:10.1371/journal.pone.0031334
- Snell, Christopher R; Van Ness, J Mark; Strayer, David R; Stevens, Staci R (2005), "Exercise capacity and immune function in male and female patients with Chronic Fatigue Syndrome (CFS)" (PDF), In Vivo, 19: 387-390, PMID 15796202
- J. Mark Vanness, Christopher R. Snell, Dean M. Fredrickson, David R. Strayer & Staci R. Stevens. (2001). Assessment of Functional Impairment by Cardiopulmonary Exercise Testing in Patients with Chronic Fatigue Syndrome. Journal of Chronic Fatigue Syndrome, Vol. 8, Iss. 3-4, pp. 103-109. http://dx.doi.org/10.1300/J092v08n03_09
- Strayer, DR; Carter, W; Strauss, KI; Brodsky, I; Suhadolnik, R; Ablashi, D; Henry, B; Mitchell, WM; Bastien, S; Peterson, D (1995), "Long Term Improvements in Patients with Chronic Fatigue Syndrome Treated with Ampligen", Journal of Chronic Fatigue Syndrome, 1 (1): 35-53, doi:10.1300/J092v01n01_04
- Ablashi DV, Berneman ZN, Williams M, Strayer DR, Kramarsky B, Suhadolnik RJ, Reichenbach N, Hiltzges P, Komaroff AL. (1994). Ampligen inhibits human herpesvirus-6 in vitro. In Vivo, 8 (4):587-91. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/7893986
- Strayer, DR; Carter, WA; Brodsky, I; Cheney, P; Peterson, D; Salvato, P; Thompson, C; Loveless, M; Shapiro, DE; Elsasser, W (1994), "A controlled clinical trial with a specifically configured RNA drug, poly(I).poly(C12U), in chronic fatigue syndrome", Clinical Infectious Diseases, 18 (Suppl 1): S88-95, PMID 8148460