- My paper (with Dr. Pruitt) on patterns of glioblastoma recurrence brought about localized irradiation to treat this disease and created the rationale for radiosurgery and locally administered therapies.
- I provided the first intra-arterial therapy of glioblastoma. This was followed by current arterial therapy with lysis of the blood-brain barrier as well as local administrations of chemotherapy.
- I identified (The New England Journal of Medicine) first evidence of the relationship between Epstein-Barr viral infections and primary lymphoma of the nervous system. Currently this virus is active in over 95% of patients with immunosuppression and primary brain lymphoma.
- My reviews of Primary Central Nervous System Lymphoma (PCNSL) provided the springboard for current clinical trials in the field.
- My papers with Fellows, on the use of high-dose methotrexate by vein to treat PCNSL provided the basis for the single most commonly used agent to treat this disease.
- I designed (for CTEP) the pivotal trial of Tykerb to treat breast metastases to brain.
- I founded the modern clinic to provide brain tumor therapy (Neuro-Oncology) at the Massachusetts General Hospital.
- Our NIH Program Project activities (Skog, Breakefield) led to the modern exploration of exosomal mutations in the biofluids of glioma patients. From these activities there emerged the International ISEV meeting held in Boston in April 2013 as well as the NIH Director’s Common Fund RFA for tumor-related exosomes.
Technological and Scientific Innovations
- The Program Project that I led created the basis for viral vector therapy with pro-drug activating transgenes.
- I hold a patent1 for a device to measure the tremor, bradykinesia and angular movement of parkinsonism.
- I hold a patent2 for the use of Epstein-Barr viral vectors specific for EBNA-1.
- I was one of the first scientists to use high-dose chemotherapy with autologous bone marrow support to treat malignant brain tumors.
- I was one of the first scientists to use intra-arterial drug administration to treat glioblastoma.
- The current 20 institution glioma Biomarking Consortium (supported by ABC2 Foundation) reflects the productivity of our PO-1 activities.
1Measuring movement disorders
- US Patent 5562104 (Hochberg, Fred H., Trustman, John W., Hochberg, Benjamin A., Brobst, Stephen A.)
I designed a technique to measure parkinsonian rigidity and tremor and bradykinesia. My colleagues and I developed the tablet methodology and mathematical algorithm to adopt this for patient use in both idiopathic parkinson’s disease and Manganese-induced movement disorders. We made use of this to evaluate afflicted miners in Chile. The technology has since been expanded to PDA and three dimensional movement analyses. The technology will ultimately replace ‘observer’ measures of these afflictions.
2Non-defective Epstein-Barr viral vector
- US Patent 6544781 (Jiang, Xiaoqun, Chiocca, E. Antonio, Kieff, Elliott, ,Wang, Fred, Hochberg, Fred)
Based upon my identification of Epstein-Barr virus (EBV) genomic material in brain lymphoma and the program project (Gene Therapy for Brain Tumor) of which I am the PI, I stimulated the creation of a viral vector system derived from EBV, where the transgene is effectively inserted into the EBV major internal repeat region (IR1) without adverse affect on EBV latent or lytic function. The vector of the invention can target and stably transform B-lymphocyte cells, both in culture and in vivo.