Studies treating benign dermal neurofibromas on the skin or just beneath the skin applying Photodynamic Therapy (PDT) continue to be performed by Dr. Whelan’s team. The studies are performed at the Medical College of Wisconsin (MCW) in affiliation with Children’s Hospital of Wisconsin (CHW) and the Froedtert Hospital (adults). They are steadily producing VERY encouraging results.
The Phase I Adult studies were completed with GOOD results, AND the gifts keep giving with time. Phase II is beginning and based on Phase I adult results, the NF Studies are deemed safe to graduate to pediatric and young adult studies.
PHASE I ADULT STUDY SUMMARY
19 patients were treated. Phase I focused on refining the protocol and equipment for treating NF tumors on adult patients. Both the skin and sub-dermal tumors show up as surface mole-like bumps of various size, that sparsely to densely populate the skin. The tumors can occur on the arm, face, or other places; a significant problem – cosmetically, medically, and psychosocially.
The following photo typifies the challenge –
Figure 1 – Typical Surface Neurofibromas
Team Whelan’s VISION is to treat the NF skin tumors using Photodynamic Therapy (PDT) when the tumors are still barely apparent. Should they be successful, Children will be spared cosmetic, medical, and psychosocial pains from readily visible NF tumors. Children are especially vulnerable to the psychosocial pain; teasing and exclusion by peers can be devastating for these youngsters.
The results of Phase I Adult Studies PDT are VERY promising. PDT PREFERENTIALLY kills the tumor cells and spares healthy cells! Not only are the NF cells killed, but observations after the treatment show a potential additional bonus. The mole-like bumps appear to shrink and flatten significantly within 3 months of treatment; however, at this point more data are needed for confirmation. If confirmed, this will be an additional gift that was not expected! The possibilities are extremely exciting!
SHORT SUMMARY OF PDT PROTOCOL
1. Levulan Keratstick (ALA, common treatment dermatologists use for keratosis) is being adapted for NF tumor treatment, PDT.
2. ALA is topically applied to tumors that are pretreated with micro-needling which makes tiny breaks in the skin. Once diffused into the cells the ALA converts to a light sensitive form called PpIX. When the PpIX is exposed to Near Infrared (NIR) 630 nm light, free radical oxygen is formed which kills the tumor cells.
3. An unexpected fortuitous finding during Phase I is that the ALA ONLY converts to PpIX in the tumor cells and NOT the healthy cells!! Thus NF cells are selectively killed, an amazing discovery!
4. The PDT treatment is painful but tolerated by most, one patient out of 19 suspended treatment. Dr. Olasz (Performs the PDT) sympathetically says – “no pain, no gain”.
5. Hopefully the significant gain will make any downsides worthwhile.
POST TREATMENT PHOTOS
The photos in Figure 1 below were taken at intervals up to 3 months after PDT treatment. As noted above, the tumors appear to be shrinking and flattening with time. Hopefully more data will scientifically validate this perception. At this time, Dr. Olasz thinks that any shrinking may be more remarkable with the surface skin tumors as opposed to the subsurface tumors.
Figure 2. Date of Treatment to 3 Months Hence
PHASE I ADULT STUDIES TUNEL ASSAY RESULTS
TUNEL assays are objective proof of the pudding. The actual number of tumor cells that are dead or dying are counted on very thin slices of NF tumor tissue. The Phase I Adult studies included bonafide treatments and placebo treatments on the same patient. TUNEL Assay evaluations were done and compared for treated and placebo tumor tissue from 5 patients.
The results are remarkable! The numbers of DEAD OR DYING cells counted are 42.5 ± 8.9 for treated and 1.13±0.64 for placebo. For two patients the kill count for the placebos was virtually 0. These data show that the PDT using ALA decidedly kills significant number of NF cells.
SOCIETY FOR INVESTIGATIVE DERMATOLOGY PAPER
Dr. Edit Olasz presented a paper entitled “Photodynamic Therapy for Benign Neurofibromas” at the 2015 meeting in Atlanta of the Society for Investigative Dermatology. The paper summarizes the Phase I Adult NF Study, see the abstract. See the abstract of this paper. The paper was well received. There were detailed questions re: the NF tumor cells that were dying.
PHASE II PEDIATRIC STUDIES
Phase II pediatric studies have begun. We will report on that later.